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Results for “Cellular differentiation”

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PubMed1999

Possible role of phospholipase D in cellular differentiation and apoptosis.

Phospholipase D (PLD) is widely distributed in mammalian cells and is implicated in a variety of physiological processes that reveal it to be a member of the signal transducing phospholipases. Recently, two related PLD isozymes, PLD1 and PLD2, were cloned. The former activity is regulated in vitro by protein kinase C and small molecular weight GTP-binding proteins (Arf and Rho family). By contrast, the basal activity of the latter is high and it is unresponsive in vitro to these activators. The cellular PLD activity and mRNA levels of these PLD isozymes drastically changed during differentiation and apoptosis in several types of cells. The general trend was that the mRNA level of PLD1 increased during differentiation, as did the observed GTP gamma S-dependent PLD activity which presumably derived from PLD1-specific catalysis. In contrast, the PLD activity and mRNA level of PLD1 were down-regulated during apoptosis. In addition to these PLD isozymes, there exists another PLD isozyme which is activated by unsaturated fatty acids such as oleic acid, although its molecular nature and physiological roles are not well defined. We have observed that this type of PLD activity is drastically increased during apoptosis of Jurkat T cells, which mainly possess this kind of PLD activity. These results suggest the possibility that PLD activity is controlled at the transcriptional level in certain circumstances, and that PLD plays roles in differentiation, survival and apoptosis in mammalian cells.

Animals↗

PubMed1988

Gastrointestinal stromal tumors. An immunohistochemical study of cellular differentiation.

Forty-five benign and 11 malignant gastrointestinal stromal tumors (GIST) were immunohistochemically studied for the presence of desmin, muscle actins (MA) and S-100 protein. To facilitate the analysis, the tumors were divided into four groups by light microscopy: (1) typical leiomyomas comparable to peripheral leiomyomas (n = 9); (2) cellular spindle cell tumors (n = 29); (3) round cell tumors ("leiomyoblastomas" n = 7); and (4) sarcomas (n = 11). The typical leiomyomas were desmin- and MA-positive throughout, and showed well-differentiated smooth muscle cells by electron microscopy, similar to the normal gastric smooth muscle cells. All esophageal leiomyomas belonged to this group. Nineteen of 29 of the Group 2 tumors showed desmin positivity and 20 of 29 showed MA positivity, but usually only in less than 10% of the tumor cells, and in many instances it was very difficult to determine whether the positive cells were real tumor cells or entrapped muscle cells. Only 5 of 29 of Group 2 tumors showed widespread desmin positivity and 11 of 29 showed similar MA positivity. Of round cell tumors, only 1 of 7 showed desmin-positive cells and 3 of 7 MA-positive cells. None of the sarcomas showed desmin, while MA positivity was found in 6 of 11 cases, often in a large number of tumor cells. Seven tumors showed a significant number of S-100 positive tumor cells, but four of these also showed a high number of desmin- and MA-positive cells, suggesting that these tumors represented complex proliferations of muscle and Schwann cell elements. Two purely S-100 positive benign probably Schwann cell-like tumors were found, both in the small bowel. Small number of S-100 positive cells were commonly found in GIST, and these probably represented entrapped Schwann cells, because many tumors showed simultaneous proliferation of non-neoplastic nerves.

Actins↗

PubMed1989

Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation.

Introduction of an exogenous retinoblastoma (RB) gene in RB-deficient retinoblastoma or osteosarcoma cells has been shown to suppress their neoplastic phenotype. In experiments designed to explore the potential mechanism of RB tumor suppression, we report here that the phosphorylation state of RB protein is modulated during normal cellular events. In resting cells, RB protein is present in its least phosphorylated form; in rapidly proliferating cells, RB protein is highly phosphorylated. Maximal phosphorylation is associated with S phase of the cell cycle. Induction of differentiation in several human leukemia cell lines by treatment with phorbol ester or retinoic acid leads to dephosphorylation of RB. Time course studies indicate that RB dephosphorylation precedes the total arrest of cell growth during differentiation. These observations strongly suggest that the function of RB protein is modulated by a phosphorylation/dephosphorylation mechanism during cell proliferation and differentiation.

Animals↗

PubMed1994

The control of spatial organization during cellular differentiation.

Caulobacter crescentus is a dimorphic bacterium that yields two distinct cell types with every cell division, a motile swarmer cell and a sessile stalked cell. Caulobacter, therefore, possesses a simple developmental program and is used as an model system to determine basic mechanisms of cellular morphogenesis. The generation of the asymmetric predivisional cell requires the temporal expression of many genes as well as the precise intracellular positioning of these gene products. Analysis of the biogenesis and positioning of cell type-specific genes and proteins has been instrumental in understanding the underlying principles as to how asymmetry in the predivisional cell is generated. This manuscript explores our current understanding of the mechanisms by which Caulobacter differentiation is achieved.

Bacterial Proteins↗

PubMed2003

Differential cellular gene expression induced by hepatitis B and C viruses.

Hepatitis B virus (HBV) is a hepatotropic virus that causes acute and chronic hepatocellular injury and hepatocellular carcinoma. To clarify how HBV proteins regulate host cellular gene expression, we used our in-house cDNA microarray and HepG2.2.15 cells, which are derived from HepG2 cells and produce all HBV proteins. Of 2304 genes investigated, several genes were differentially expressed in HepG2.2.15 cells compared with HepG2 cells. These genes included insulin-like growth factor II and alpha-fetoprotein, consistent with previous reports. Furthermore, we previously performed similar microarray analyses to clarify the effects of hepatitis C virus (HCV) proteins on host cells, using a HepG2-derivative cell line, which produces all HCV proteins. Using these two microarray results, we compared the differences in cellular gene expression induced by HBV and HCV proteins. The expression of the majority of genes investigated differed only slightly between HBV and HCV protein-producing cells. However, HBV and HCV proteins clearly regulated several genes in a reciprocal manner. Combined, these microarray results shed new light on the effects of HBV proteins on cellular gene expression and on the differences in the pathogenic activities of these two hepatitis viruses.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Cellular differentiation in the process of generation of the eukaryotic cell.

Primitive atmosphere of the earth did not contain oxygen gas (O2) when the proto-cells were generated successfully as the result of chemical evolution and then evolved. Therefore, they first had acquired anaerobic energy metabolism, fermentation. The cellular metabolisms have often been formed by reorganizing to combine or recombinate between pre-existing metabolisms and newly born bioreactions. Photosynthetic metabolism in eukaryotic chloroplast consists of an electron-transfer photosystem and a fermentative reductive pentose phosphate cycle. On the other hand, O2-respiration of eukaryotic mitochondrion is made of Embden-Meyerhof (EM) pathway and tricarboxylic acid cycle, which originate from a connection of fermentative metabolisms, and an electron-transfer respiratory chain, which has been derived from the photosystem. These metabolisms already are completed in some evolved prokaryotes, for example the cyanobacterium Chlorogloea fritschii and aerobic photosynthetic bacteria Rhodospirillum rubrum and Erythrobacter sp. Therefore, it can be reasonably presumed that the eukaryotic chloroplast and mitochondrion have once been formed as the result of metabolic (and genetic) differentiations in most evolved cyanobacterium. Symbiotic theory has explained the origin of eukaryotic cell as that in which the mitochondrion and chloroplast have been derived from endosymbionts of aerobic bacterium and cyanobacterium, respectively, and has mentioned as one of the most potent supportive evidences that amino acid sequences of the photosynthetic and O2 -respiratory enzymes show similarities to corresponding prokaryotic enzymes. However, as will be shown in this discussion, many examples have shown currently that prokaryotic sequences of informative molecules are conserved well not only in those of the mitochondrial and chloroplast molecules but also in the nuclear molecules. In fact, the similarities in sequence of informative molecules are preserved well among the organisms not only in phylogenetically close relationships but also under highly selective pressure, that is under a physiological constraint for the species in their habitats. Therefore, the similarities in amino acid sequences of proteins between the prokaryotes and the organelles are not necessarily direct evidence for their phylogenetical closeness: it gives still less evidence for a symbiotic relationship between the prokaryotes and the organelles. The metabolic compartmentalization of the membranes is an important tendency in cellular evolution to guarantee high specificity and rate of the metabolisms. It is suggested from the data that the intracellular membranes are not static but undergo dynamic turnover. Furthermore, these facts strongly support the Membrane Evolution Theory which was proposed by one of the authors in 1975.

Amino Acid Sequence↗

PubMed1995

Transforming growth factor alpha disrupts the normal program of cellular differentiation in the gastric mucosa of transgenic mice.

Transforming growth factor alpha (TGF alpha) evokes diverse responses in transgenic mouse tissues in which it is over-expressed, including the gastric mucosa, which experiences aberrant growth and a coincident repression of hydrochloric acid production. Here we show that ectopically expressed TGF alpha induces an age-dependent cellular reorganization of the transgenic stomach, in which the surface mucous cell population in the gastric pit is greatly expanded at the expense of cells in the glandular base. Immunohistochemical analysis of BrdU incorporation into DNA demonstrated that although mature surface mucous cells were not proliferating, DNA synthesis was enhanced by approximately 67% in the glandular base and isthmus, where progenitor cells reside. RNA blot and in situ hybridization were employed to determine temporal and spatial expression patterns of specific markers representing a variety of exocrine and endocrine gastric cell types. Mature parietal and chief cells were specifically depleted from the glandular mucosa, as judged by a 6- to 7-fold decrease in the expression of genes encoding H+,K(+)-ATPase, which is required for acid secretion, and pepsinogen C, respectively. The reduction of these markers coincided in time with the activation of TGF alpha transgene expression in the neonatal stomach. The rate of cell death in the glandular region was not overtly different. Significantly, the loss of parietal and chief cells occurred without a concomitant loss of their respective cellular precursors. In contrast to exocrine cells, D and G endocrine cells were much less severely affected, based on analysis of somatostatin and gastrin expression. Analysis of these dynamic changes indicates that TGF alpha can induce selective alterations in terminal differentiation and proliferation in the gastric mucosa, and suggests that TGF alpha plays an important physiological role in the normal regulation of epithelial cell renewal.

Animals↗

PubMed1999

Measles virus replication in cells of myelomonocytic lineage is dependent on cellular differentiation stage.

Measles virus (MV)-infected monocytes may have a central role in virus-induced immunosuppression. Our understanding of MV replication in monocytic cells is, however, incomplete. In this work we have investigated MV replication in cells of human myelomonocytic lineage with different maturation stages in order to study the effect of cellular maturation on virus infection. MV was able to infect human bone marrow myeloid granulocyte-macrophage colony-forming cells (CFC-GM) as well as monocytes and macrophages, but the replication cycle seemed to be regulated by the maturation stage of the cells. Virus infection in CFC-GM was productive, unlike in monocytes and macrophages, where an extensive viral RNA synthesis occurred and high amounts of proteins were synthesised without a remarkable release of infectious virus. Efficiency of viral macromolecular synthesis in macrophages was comparable to that of promonocytic cell line U-937 and human epithelial cell line A549, but in contrast to macrophages the cell lines highly supported productive infection. On the other hand, chemically induced maturation of the human promyelocytic and promonocytic cell lines HL-60, THP-1, and U-937 to more mature macrophage-like forms did not markedly alter the replication cycle of MV in these cell lines. Our results showed that MV replication in myelomonocytic cells varied depending on the maturation stage of the cells. The immature myelomonocytic cells supported productive virus infection, but the maturation process lead to cellular changes that caused a restriction of MV replication cycle partly at posttranscriptional and partly at posttranslational level. The metabolic milieu of monocytes and macrophages as such was sufficient to support extensive viral macromolecular synthesis.

Blotting, Western↗

PubMed1995

The expression of ferritin on renal cancers and its relationship with cellular differentiation and tumour stage.

OBJECTIVES: To investigate ferritin expression in renal carcinoma and the correlation of expression with tumour differentiation and stage. PATIENTS AND METHODS: Ferritin was immunohistologically detected in 35 patients (23 men and 12 women; mean age 58.2 years, range 40-82) with renal carcinoma and the findings compared with cellular type, tumour stage and the ferritin expression of a similar control population of 16 patients. RESULTS: The incidence of ferritin expression in renal carcinomas was 51%. Expression was significantly related to tumour stage and not cellular type. CONCLUSION: The results of this study re-emphasize the high expression of ferritin in renal cell carcinoma and the correlation of expression with tumour behaviour.

Adenocarcinoma↗

PubMedDate not supplied

Protein synthesis patterns of Paracoccidiodes brasiliensis isolates in stage-specific forms and during cellular differentiation.

In this paper we compared the protein synthesis patterns of Paracoccidioides brasiliensis isolates. The protein profiles were compared for both yeast and mycelial forms and similarity analysis among them was performed by calculating similarity matrices and grouping the isolates in dendrograms. The examined isolates exhibited highly variable cellular morphology at 36 degrees C, when typical yeast cells were expected. On the other hand, at 26 degrees C all the isolates showed mycelial morphology. The analysis of protein synthesis profiles made it possible to cluster the P. brasiliensis isolates into groups that correlated with the morphological data. Interestingly, growth at 36 degrees C strongly decreased the heterogeneity of protein synthesis patterns seen in mycelial isolates. It was possible to cluster the isolates grown at 36 degrees C in three groups based on their two-dimensional protein synthesis analysis. The similarity index observed among the mycelial isolates was lower than that obtained with yeast cells, suggesting a more homogenous gene expression pattern in the host-adapted form than in the saprobic phase.

Electrophoresis, Gel, Two-Dimensional↗

PubMed1988

[Cellular differentiation in storiform-pleomorphic malignant fibrous histiocytomas. An electron microscopic study of histogenesis].

The most common form of malignant fibrous histiocytoma is the storiform-pleomorphic subtype composed of spindle-shaped fibroblast-like cells, mononucleated histiocytic elements and a changing amount of pleomorphic giant cells. In relation to the changing cellular structures 14 pleomorphic-storiform malignant fibrous histiocytomas were investigated electronmicroscopically. In all tumors several types of cells varying in shape, and size as well as in organelle composition could be demonstrated: 1. Undifferentiated cells, which are relatively small and have a scanty cytoplasm with few organelles. 2. Fibroblast-like cells with well developed rough endoplasmic reticulum, mostly arranged in a storiform pattern. 3. Myofibroblasts corresponding to fibroblasts and showing bundles of thin filaments (4 to 6 nm) with focal dense bodies in the peripheral area of the cytoplasm. 4. Histiocyte-like cells characterized by filopodia-like projections and abundant cytoplasm containing lysosomes and phagolysosomes and also lipid droplets. 5. Chimeric cells, which are intermediate forms with features of fibroblast-like and histiocyte-like tumor cells. 6. Multinucleated tumor giant cells which can be subdivided into fibroblast-like and histiocyte-like types and intermediate forms. On the basis of our ultrastructural studies the storiform pleomorphic malignant fibrous histiocytoma is interpreted as a tumor of an undifferentiated mesenchymal cell with the potency of fibroblastic or histiocytic differentiation. The origin of this cell is uncertain. Dedifferentiation of a differentiated connective tissue cell (fibroblast, pericyte) into a proliferating undifferentiated precursor cell is discussed.

Cell Differentiation↗

PubMed1998

Differentiated cellular function in fetal chondrocytes cultured with insulin-like growth factor-I and transforming growth factor-beta.

This study examined fetal chondrocyte proliferation and function following exposure to transforming growth factor-beta and insulin-like growth factor-I. Fetal equine articular chondrocytes of the early third-trimester were isolated and cultured in monolayer conditions, then exposed to 0, 1, 5, or 10 ng/ml transforming growth factor-beta or 0, 10, 50, or 100 ng/ml insulin-like growth factor-I for 48 hours. Proliferative responses were assessed by cell counts and [3H]thymidine uptake into precipitable DNA. Differentiated chondrocyte metabolic activity was determined by sulfated glycosaminoglycan quantitation, 35[SO4] incorporation into precipitable glycosaminoglycan, and proteoglycan molecular sizing by CL-2B column chromatography. Morphological changes seen on phase-contrast microscopy included a larger proportion of rounded cells in monolayer cultures supplemented with insulin-like growth factor-I and cytotoxic changes in cells treated with transforming growth factor-beta. Both insulin-like growth factor-I and transforming growth factor-beta resulted in significant elevations of [3H]thymidine uptake; however, cell numbers did not rise sufficiently over the 48-hour culture period to reach significant levels. Maximum mitogenic responses were evident at 50 and 100 ng/ml insulin-like growth factor-I and 5 ng/ml transforming growth factor-beta. The production of proteoglycan was also enhanced (435%) by exposure to 50 ng/ml insulin-like growth factor-I, and an increased proportion of larger proteoglycan monomer species was evident in cultures treated with 50 and 100 ng/ml insulin-like growth factor-I. A similar dose-response was also evident in cultures treated with transforming growth factor-beta (maximal 164% increase with 5 ng/ml), although the presence of serum in the culture medium altered the pattern of enhanced proteoglycan synthesis to favor the lower concentration of 1 ng/ml (191%). Additionally, larger proteoglycan molecules were synthesized in response to high concentrations of transforming growth factor-beta in serum-free cultures. Significant biochemical changes resulted from the addition of transforming growth factor-beta to fetal chondrocyte cultures; however, monolayer cultures that were treated with transforming growth factor-beta and supplemented with serum began to develop cellular toxicity, including nuclear pyknosis and cytoplasmic fragmentation. Degenerative cellular changes were not evident in cultures treated with insulin-like growth factor-I, and significant differentiated metabolic activity resulted from the presence of insulin-like growth factor-I in the culture medium. These data suggest that the responses of fetal chondrocytes to insulin-like growth factor-I and transforming growth factor-beta were enhanced compared with the responses of chondrocytes derived from postnatal animals and that these metabolically active cells can be primed by endogenous or exogenous growth factors to provide enhanced articular function and repair.

Animals↗

PubMed1997

Tumor progression and cellular differentiation of pulmonary adenocarcinomas in SV40 large T antigen transgenic mice.

Transgenic mice harboring the SV40 early region genes under transcriptional control of regulatory regions from the human surfactant protein C (SP-C) gene were used to study the progression of pulmonary adenocarcinomas in vivo. SP-C/SV40 early region gene (SP-C/TAg) transgenic mice consistently developed pulmonary adenocarcinomas. Distinct neoplasia was first detected at 4 wk of age and large tumor nodules were observed by 20-29 wk of age. SV40 large T mRNA was detected in distal bronchiolar and alveolar epithelial cells prior to tumor formation and in neoplastic cells at all stages of tumor development. SV40 large T mRNA correlated with cyclin-dependent kinase 1 (cdk1) mRNA expression, a marker of cellular proliferation. The nonciliated bronchiolar cell marker, CC10 mRNA, was detected in the majority of lung tumors at all ages, but was consistently decreased in the larger tumor nodules at later stages of tumor progression. CC10 mRNA was not detected in multiple murine lung epithelial (MLE) cell lines derived from the SP-C/TAg mice when cultured in vitro; but was induced in the MLE-15 clonal cell line when propagated in vivo in the flanks of nude mice. SP-C mRNA, an alveolar Type II cell marker, was also expressed in the MLE-15 cells when grown in nude mice. However, CC10 and SP-C mRNAs were expressed in distinct, nonoverlapping regions of the MLE-15 tumors. These studies support the concept that tumor progression is associated with changes in respiratory epithelial cell differentiation, and that the expression of bronchiolar and alveolar cell specific markers can be induced in a clonal cell line with changes in cellular environment.

Adenocarcinoma↗

PubMed1999

Differential cellular and subcellular localization of protein phosphatase 1 isoforms in brain.

Protein phosphatase 1 (PP1) is a gene family with a number of important functions in brain. Association with a wide variety of regulatory/targeting subunits is thought to be instrumental in directing the phosphatase to specific subcellular locations and substrates. By using antibodies directed against specific PP1 isoforms, we asked whether PP1 isoforms are differentially distributed in brain. Immunoblotting detects in brain the PP1gamma2 isoform, which had previously been thought to be testis specific, in addition to alpha, beta, and gamma1 isoforms. PP1 isoform expression varies modestly in extracts from different subdissected brain regions and is relatively constant during postnatal development, except for an about twofold increase in PP1gamma2. By immunohistochemical analyses of rat brain, PP1beta and PP1gamma1 cellular expression is widespread but quite distinct from one another. Subcellular fractionation studies demonstrate that PP1beta and PP1gamma1 are selectively associated with different cytoskeletal elements: PP1beta with microtubules, PP1gamma1 with the actin cytoskeleton. Double-immunofluorescence labeling of cultured cortical neurons further reveals a strikingly different and nonoverlapping localization of PP1beta and PP1gamma1: whereas PP1beta localizes to a discrete area of the soma, PP1gamma1 is highly enriched in dendritic spines and presynaptic terminals of cultured neurons. These results show that PP1 isoforms are targeted to different neuronal cytoskeletal compartments with a high degree of specificity, presumably by isoform-specific association with regulatory/targeting proteins. Furthermore, the synaptic localization of PP1gamma1 indicates that it is this isoform that is involved in the regulation of synaptic phosphoproteins such as neurotransmitter receptors and ion channels implicated in synaptic plasticity.

Animals↗

PubMed2004

Form follows function: The genomic organization of cellular differentiation.

The extent to which the nucleus is functionally organized has broad biological implications. Evidence supports the idea that basic nuclear functions, such as transcription, are structurally integrated within the nucleus. Moreover, recent studies indicate that the linear arrangement of genes within eukaryotic genomes is nonrandom. We suggest that determining the relationship between nuclear organization and the linear arrangement of genes will lead to a greater understanding of how transcriptomes, dedicated to a particular cellular function or fate, are coordinately regulated. Current network theories may provide a useful framework for modeling the inherent complexity the functional organization of the nucleus.

Animals↗

PubMed1996

Gravitropism of the primary root of maize: a complex pattern of differential cellular growth in the cortex independent of the microtubular cytoskeleton.

The spatio-temporal sequence of cellular growth within the post-mitotic inner and outer cortical tissue of the apex of the primary root of maize (Zea mays L.) was investigated during its orthogravitropic response. In the early phase (0-30 min) of the graviresponse there was a strong inhibition of cell lengthening in the outer cortex at the lower side of the root, whereas lengthening was only slightly impaired in the outer cortex at the upper side. Initially, inhibition of differential cell lengthening was less pronounced in the inner cortex indicating that tissue tensions which, in these circumstances, inevitably develop at the outer-inner cortex interface, might help to drive the onset of the root bending. At later stages of the graviresponse (60 min), when a root curvature had already developed, cells of the inner cortex then exhibited a prominent cell length differential between upper and lower sides, whereas the outer cortex cells had re-established similar lengths. Again, tissue tensions associated with the different patterns of cellular behaviour in the inner and outer cortex tissues, could be of relevance in terminating the root bending. The perception of gravity and the complex tissue-specific growth responses both proceeded normally in roots which were rendered devoid of microtubules by colchicine and oryzalin treatments. The lack of involvement of microtubules in the graviresponse was supported by several other lines of evidence. For instance, although taxol stabilized the cortical microtubules and prevented their re-orientation in post-mitotic cortical cells located at the lower side of gravistimulated roots, root bending developed normally. In contrast, when gravistimulated roots were physically prevented from bending, re-oriented arrays of cortical microtubules were seen in all post-mitotic cortical cells, irrespective of their position within the root.

Cell Size↗

PubMed1990

Liver fatty acid-binding protein: a marker for studying cellular differentiation in gut epithelial neoplasms.

Human liver fatty acid binding protein is a 127 residue cytoplasmic protein synthesized in liver and in the intestinal epithelium. Previous studies of normal and transgenic mice indicated that the liver fatty acid-binding protein gene is a sensitive marker of enterocytic differentiation. This study shows the use of immunohistochemical methods to examine liver fatty acid-binding protein gene expression in normal human colonic epithelium, colonic villoglandular adenomas, nonmucinous and mucinous adenocarcinomas, and several types of noncolonic epithelial neoplasms. Cells containing liver fatty acid-binding protein were found in normal colonic epithelium, in two thirds of colorectal villoglandular adenomas and nonmucinous adenocarcinomas, and in one third of mucinous adenocarcinomas but not in noncolonic, nonhepatic carcinomas. All liver fatty acid-binding protein-positive colonic adenomas and adenocarcinomas contained patches of immunoreactive cells distributed among histologically identical patches of cells without liver fatty acid-binding protein immunoreactivity. This "mosaicism" was also found in metastases from liver fatty acid-binding protein-positive colonic adenocarcinomas. Immunostaining of these liver fatty acid-binding protein-positive tissues for carcinoembryonic antigen did not show a mosaic cellular pattern in its expression. These data suggest that within a given neoplasm, differences exist in the differentiation programs of monoclonally-derived, malignant colonic epithelial cells and that liver fatty acid-binding protein is a useful marker for operationally defining these subpopulations. Liver fatty acid-binding protein is also a potentially useful diagnostic marker for colorectal and hepatic carcinomas.

Adenocarcinoma↗

PubMed2003

Does metabolic radiolabeling stimulate the stress response? Gene expression profiling reveals differential cellular responses to internal beta vs. external gamma radiation.

DNA microarray analyses were used to investigate the effect of cell-incorporated 35S-methionine on human colorectal carcinoma cells. This beta-radiation-induced gene expression profile was compared with that induced by external gamma-radiation. The extent of DNA fragmentation was used as a biomarker to determine the external gamma dose that was bioequivalent to that received by cells incubated in medium containing 35S-methionine. Studies showed that 35S-methionine at 100 microCi/mL induced a much more robust transcriptional response than gamma-radiation (2000 cGy) when evaluated 2 h after the labeling or irradiation period. The cellular response to internal beta-radiation was greater not only with respect to the number of genes induced, but also with respect to the level of gene induction. Not surprisingly, the induced genes overlapped with the set of gamma-responsive genes. However, a distinct beta-gene induction profile that included a large number of cell adhesion proteins was also observed. Taken together, these studies demonstrate that metabolic incorporation of a low energy beta-emitter, such as 35S-methionine, can globally influence a diverse set of cellular activities that can, in turn, affect the outcome of many experiments by altering the cell cycle, metabolic, signaling, or redox status (set point) of the cell. Additional studies of the mechanism of beta-induced proliferation arrest and cell death and of the significance of its differential gene induction/repression profile in comparison to pulsed gamma-irradiation may lead to new insights into the ways in which ionizing radiation can interact with cells.

Beta Particles↗