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R Hass

Publications and source records attributed to R Hass.

At least 19 recordsLinked to original sources
PubMed2006

Antenatal ultrasonographic appearance of isolated fetal ascites. A case report of sinus urogenitalis.

BACKGROUND: Isolated fetal ascites can be caused by many heterogeneous disorders and is associated with a variety of conditions. Cloacal anomalies are rare abnormalities with a highly variable array of sonographic symptoms, which make them difficult to diagnose antenatally. We present a case with isolated fetal ascites without hydronephrosis caused by a cloacal malformation. CASE: A 28-year-old woman, gravida 2, para 1, was referred to our unit at 18 weeks gestation with a hyperdense structure in the fetal liver. Cordocentesis revealed a normal karyotype and negative viral titers. Isolated fetal ascites occurred for the first time at 23 weeks gestation. Serial ultrasounds showed progressive fetal ascites with no hydronephrosis at any time and no other malformations apart from the previously diagnosed hyperechogenic liver structure. After the insertion of an abdomino-amniotic shunt, a temporary reduction of the sonographically detectable ascites could be achieved. Cesarean delivery was necessary due to a pathological CTG at 33 weeks of gestation. The baby was born with a markedly distended abdomen. Postnatal radiologic examination showed two fistulae between the cloaca and the notedly dilated vagina and the rectum respectively. At the age of 3 months a vaginoplasty was performed, which involved creating a correctly positioned vaginal opening, reconstruction of the urethra and rectum as well as occlusion of the two fistulae. CONCLUSION: In view of the examinations, performed before and after delivery, it has to be assumed that fetal urine drained via the cloaca through the fallopian tubes into the abdomen. In contrast to usual appearance of cloacal malformations no hydronephrosis was detected and the kidney function was normal at all times. To our knowledge, this is the first published case of isolated fetal ascites without hydronephrosis caused by a cloacal malformation.

Adult↗
PubMed2003

Increased oxidative stress in pre-eclamptic placenta is associated with altered proteasome activity and protein patterns.

Analysis of the amount of oxidatively damaged proteins in placenta proteins from normal pregnancies and pre-eclampsia revealed a relative increase of about 30 per cent of damaged proteins in pre-eclamptic placenta. Previous work has demonstrated that these cell- and tissue-damaging oxidatively stressed proteins are metabolized particularly by the 20S proteasome. Evaluation of the proteasomal activity revealed a significantly reduced proteasome function in pre-eclamptic placenta by about 30 per cent, suggesting that the accumulation of oxidatively damaged proteins in pre-eclampsia is associated with reduced proteasomal activity. To investigate these effects at molecular levels, separation of placental proteins by two-dimensional SDS-PAGE and subsequent anti-proteasome Western blot revealed several sets of approximately 20 kDa and 30 kDa protein subunits in normal placenta which appear at low or undetectable expression levels in pre-eclamptic placenta. Control Western blots against the placenta protein 14 (PP14) demonstrated equal loading and no significant differences in the PP14 protein patterns. These data suggested that alteration of the multifactorial proteasomal protein complex in pre-eclamptic placenta is accompanied by reduced metabolization of oxidatively damaged proteins. Consequently, the accumulation of these damaged proteins in the placenta may be associated with metabolic interference and thus contribute to certain developments of pre-eclampsia. Silver staining of the two-dimensional SDS-PAGE revealed a variety of acidic proteins in the range of 20 kDa and 45 kDa, respectively, which are differentially expressed in normal and pre-eclamptic placenta and thus provide further analytic potential for metabolic interference.

Carbon Dioxide↗
PubMed2001

Regulation of the nuclear proteasome activity in myelomonocytic human leukemia cells after adriamycin treatment.

Treatment of different human leukemia cell variants with the anthracycline adriamycin was associated with a rapid activation of the proteasome. Thus, proliferating U937, TUR, and retrodifferentiated U937 cells exhibited a 4.3-fold, 5.8-fold, and 4.3-fold proteasome activation within 15 minutes after adriamycin treatment, respectively. In contrast, little if any proteasome activation was detectable in a growth-arrested differentiated U937 population following adriamycin treatment. Further analysis of this mechanism revealed a significant reduction of adriamycin-induced proteasome activity after inhibition of poly(ADP-ribose) polymerase (PARP) by 3-aminobenzamide (3-ABA) in the proliferating leukemic cell types. These findings suggested that PARP is involved in the regulation of drug-induced proteasome activation. Indeed, anti-PARP immunoprecipitation experiments of adriamycin-treated cells revealed increasing levels of coprecipitated, enzymatically active proteasome particularly in the proliferating cell variants in contrast to the differentiated U937 cells, with a maximum after 15 minutes, and sensitivity to PARP inhibition by 3-ABA. The specific role of the PARP was investigated in U937 and TUR cell clones stably transfected with a constitutively active antisense PARP (asPARP) vector. Thus, asPARP-TUR cells developed a 25-fold increased sensitivity to adriamycin treatment. Furthermore, we investigated leukemic blasts isolated from acute myelogenous leukemia patients and obtained a similarly enhanced proteasome activity after adriamycin treatment, which was dependent on the PARP and thus could be coprecipitated with anti-PARP antibodies. Transient transfection of leukemic blasts with the asPARP vector significantly reduced the adriamycin-induced proteasome activation. These data suggest that the PARP-associated nuclear proteasome activation represents a potential target within chemotherapeutic defense mechanisms developed by leukemia cells.

Antineoplastic Agents↗
PubMed2000

Proteasome activation by poly-ADP-ribose-polymerase in human myelomonocytic cells after oxidative stress.

Cytotoxic action of a variety of antitumor drugs generate oxidatively modified proteins that are predominantly metabolized via the proteasome. In the present study, a differentiation-retrodifferentiation cell system was exposed to oxidative stress by hydrogen peroxide treatment. Thus, the activity of the nuclear proteasome in proliferating human U937 leukemic cells increased by 2.5-fold after hydrogen peroxide treatment. In contrast, growth-arrested differentiated U937 cells demonstrated 40% less constitutive proteasomal activity, which was not inducible after hydrogen peroxide exposure. After a retrodifferentiation process, however, in which differentiated U937 cells resume autonomous growth again, the proteasomal activity was indistinguishable from that in U937 control cells, both constitutively and after induction of oxidative stress. Moreover, cells of TUR, a differentiation-resistant U937 subclone, expressed an elevated constitutive proteasomal activity that increased by 2.5-fold after oxidative stress. Immunoblot analysis revealed that these differences in proteasomal activities did not correlate with proteasome protein expression but with protein levels of the nuclear enzyme poly-ADP-ribose-polymerase (PARP). Further studies using specific PARP inhibitors revealed that the noninducible proteasome activity in differentiated U937 cells was PARP independent, whereas the increased activity level in oxidatively stressed TUR cells was downregulated upon PARP inhibition. Immunoprecipitation experiments demonstrated a protein-protein interaction of the functional active PARP with the proteasome in correlation with the proteasome activity. Similar results were obtained by analyzing protein carbonyls after oxidative stress. Taken together, these data suggest that proliferating, rather than growth-arrested, cells metabolize oxidatively damaged nuclear proteins via the proteasome by expressing high levels of PARP.

Cell Differentiation↗
PubMed2000

Activation of protein kinase C relays distinct signaling pathways in the same cell type: differentiation and caspase-mediated apoptosis.

Activation of PKC with 5 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) for 72 h in human U937 myeloid leukemia cells is associated with induction of adherence, followed by monocytic differentiation and G0/G1 cell cycle arrest. In this study, we demonstrate that in addition to these effects about 25% of U937 cells accumulated in an apoptotic subG1 phase after TPA treatment. The appearance of these apoptotic suspension cells was detectable throughout the time course of the culture and was independent of TPA concentrations between 0.5 and 500 nM. Experiments with cells synchronized by centrifugal elutriation revealed dominant susceptibility of G1-phase cells to TPA-mediated apoptosis. While adherent cells expressed differentiation markers including the integrin CD11c, this effect was less pronounced in the TPA-treated suspension fraction. Moreover, previous work has demonstrated cell cycle arrest in differentiating U937 cells. Accordingly, PKC activation by TPA treatment was associated with a significant expression of the cdk/cyclin inhibitor p21WAF/CIP/sdi-1 in the adherent population and subsequent G0/G1 cell cycle arrest. In contrast, suspension cells failed to induce significant levels of p21WAF/CIP/sdi-1 after TPA stimulation. Immunoblotting experiments demonstrated no difference in the expression of the pro-apoptotic factors Bax, Bad, and Bak in either control U937 and TPA-treated adherent or suspension cells, respectively. However, anti-apoptotic factors including Bcl-2, Bcl-xL, and Mcl-1 were significantly induced in the adherent population whereas no induction was detectable in the suspension cells. In this context, incubation with the caspase-3/caspase-7 specific tetrapeptide inhibitor DEVD prior to TPA treatment prevented an accumulation of cells in subG1, respectively, demonstrating an involvement of these caspases. Taken together, these data suggest that PKC activation can relay distinct signaling pathways such as induction of adherence coupled with monocytic differentiation and growth arrest, or induction of caspase-mediated apoptosis coupled with the failure to adhere and to differentiate.

Annexin A5↗
PubMed1999

Poly-ADP ribose polymerase activates nuclear proteasome to degrade oxidatively damaged histones.

The 20S proteasome has been shown to be largely responsible for the degradation of oxidatively modified proteins in the cytoplasm. Nuclear proteins are also subject to oxidation, and the nucleus of mammalian cells contains proteasome. In human beings, tumor cells frequently are subjected to oxidation as a consequence of antitumor chemotherapy, and K562 human myelogenous leukemia cells have a higher nuclear proteasome activity than do nonmalignant cells. Adaptation to oxidative stress appears to be one element in the development of long-term resistance to many chemotherapeutic drugs and the mechanisms of inducible tumor resistance to oxidation are of obvious importance. After hydrogen peroxide treatment of K562 cells, degradation of the model proteasome peptide substrate suc-LLVY-MCA and degradation of oxidized histones in nuclei increases significantly within minutes. Both increased proteolytic susceptibility of the histone substrates (caused by modification by oxidation) and activation of the proteasome enzyme complex occur independently during oxidative stress. This rapid up-regulation of 20S proteasome activity is accompanied by, and depends on, poly-ADP ribosylation of the proteasome, as shown by inhibitor experiments, 14C-ADP ribose incorporation assays, immunoblotting, in vitro reconstitution experiments, and immunoprecipitation of (activated) proteasome with anti-poly-ADP ribose polymerase antibodies. The poly-ADP ribosylation-mediated activated nuclear 20S proteasome is able to remove oxidatively damaged histones more efficiently and therefore is proposed as an oxidant-stimulatable defense or repair system of the nucleus in K562 leukemia cells.

Adenosine Diphosphate Ribose↗
PubMed1999

Signaling defect in the activation of caspase-3 and PKCdelta in human TUR leukemia cells is associated with resistance to apoptosis.

Exposure of the two related human leukemic cell lines U937 and TUR to chemotherapeutic compounds resulted in opposite effects on induction and resistance to apoptosis. Incubation of U937 cells with 1-beta-d-arabinofuranosylcytosine or the etoposide VP-16 was accompanied by growth arrest in G0/G1 of the cell cycle and an accumulation of a population in the sub-G1 phase which exhibited characteristics typical for the apoptotic pathway. In contrast, human TUR leukemia cells demonstrated no significant effects after a similar treatment with Ara-C and VP-16. Thus, TUR cells continued to proliferate in the presence of these anti-cancer drugs and the number of apoptotic cells as evaluated by propidium iodide staining and the detection of internucleosomal DNA fragmentation was significantly reduced when compared to the parental U937 cells. Similar effects were observed upon serum-starvation demonstrating resistance to apoptosis in TUR cells. Whereas induction of apoptosis is regulated by a network of distinct factors including the activation of proteolytically active caspases, we investigated these pathways in both cell lines. U937 cells demonstrated activation of the 32-kDa caspase-3 upon drug treatment by cleavage into the 20-kDa activated form. However, there was no 20-kDa caspase-3 fragment detectable in TUR cells. Simultaneously, the enzymatic activity of caspase-3 was significantly increased in drug-treated U937 cells as measured in vitro by enhanced metabolization of a fluorescence substrate and in vivo by cleavage of an appropriate substrate for caspase-3, namely, protein kinase Cdelta. In contrast, there was little if any caspase-3 activation detectable in drug-treated TUR cells. Taken together, these data suggest a signaling defect in the activation of the caspase-3 proteolytic system in TUR cells upon treatment with chemotherapeutic compounds which is associated with resistance to apoptosis in these human leukemia cells.

Apoptosis↗
PubMed1999

Telomerase activity of cells during alterations of their proliferative states.

We showed that the telomerase activity (TAC) of human promyelocytic leukemic cells U-937 and HL-60 sharply decreased after induction of macrophagal differentiation. Dedifferentiation which occurred several days after removing the inductor was accompanied by the resumption of proliferation and increase of TAC. Telomerase activity significantly decreased also when U-937 cells ceased to proliferate in response to long-term inhibition of the telomerase function by azidothymidine. TAC was observed to decrease slowly for 6-8 days in the course of transition of mouse fibroblasts 3T3 Swiss to the quiescent state. TAC decreased both in serum-deprived cells and in slowly proliferating high-density inhibited cells. During the exit from quiescence and in dedifferentiation, the increase in TAC preceded the resumption of proliferation. In all the cases described the alterations of TAC correlated with alterations in the nonspecific polymerase activity which we had found earlier (D. N. Chernov, Y. E. Yegorov, and S. S. Akimov, DokL Biochemistry 349:55-58 (1996)). The problems of TAC regulation are discussed.

3T3 Cells↗
PubMed1998

Endogenous beta-galactosidase activity in continuously nonproliferating cells.

Cytochemically detectable activity of endogenous beta-galactosidase was found at pH 6.0 in Swiss 3T3 cells after long-term incubation in low serum or in the presence of heparin concentrations known to reversibly inhibit cell proliferation. A high percentage of beta-galactosidase-positive cells were detected in U937 and HL60 cultures at the late stage of macrophage-like differentiation induced by TPA. Interestingly, a small number of beta-galactosidase-positive cells were found even in the growing Swiss 3T3 cultures. These positive cells expressed morphological features similar to those of senescent cells. Thus, the activity of beta-galactosidase at pH 6.0 cannot be considered an exclusive marker of senescent cells since it is expressed in other types of nonproliferating cells.

3T3 Cells↗
PubMed1997

Aggressive tumor growth of human TUR leukemia cells is associated with high levels of c-myc expression and down-regulation of p20-max.

A sub-clone of human U937 myeloid-leukemia cells, termed TUR, was investigated with respect to its proliferative capacity in vivo and in vitro. Karyotypic analysis demonstrated certain differences in TUR cells and some monocytic properties, such as expression of alpha-naphthyl acetate esterase, were constitutively higher in TUR cells than in U937 cells. However, stimulation of both cell lines by the differentiation-inducing phorbol ester TPA revealed reduced responsiveness of TUR cells in the expression of alpha-naphthyl acetate esterase and the generation of O2(-)-anions as compared with U937 cells. Injection into scid mice resulted in potent and rapid tumor development of TUR cells: while 87% of U937-cell injections resulted in tumors after about 14 days, 100% of TUR cell injections produced a tumor after only 11 days, with a tumor area approximately 3.1-times larger than tumors generated by U937 cells. In this context, Western-blot analysis of the myc family revealed high levels of c-myc protein accumulation in TUR cells even in the presence of TPA. In contrast, incubation of U937 cells with phorbol ester was associated with progressive down-regulation of c-myc protein. c-myc can also form transcriptionally active heterodimeric complexes with the nuclear phosphoproteins p20/p22 max: thus, TPA treatment resulted in down-regulation of the p20 form of max in TUR cells. Another regulatory factor in the myc family, mad-1, was expressed unaltered in U937 and in TUR cells regardless of TPA stimulation.

Animals↗
PubMed1997

Differential effects of phorbol ester on signaling and gene expression in human leukemia cells.

Human U937 myeloid leukemia cells were treated with different concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA) to determine signals that contribute to growth arrest and differentiation. While 0.5 nM TPA had little if any effect, exposure of U937 cells to higher TPA concentrations (5-500 nM) revealed a complete growth arrest after 48 h. Cytosolic PKC activity decreased by 50% after exposure to 0.5 nM TPA and by 80 and 95% after stimulation with 5 nM and 50 nM TPA, respectively. Simultaneously, the PKC activity in the particulate fraction of U937 cells increased accordingly. These events were associated with induction of a differentiated monocytic phenotype. Expression of the c-myc gene was down-regulated and c-jun and c-fms transcripts increased following exposure to 5-500 nM TPA. In contrast, exposure to 0.5 nM TPA decreased c-myc expression and increased c-jun transcripts only transiently between 4 and 8 h while little if any effect was detectable on c-fms mRNA expression and subsequent differentiation. Taken together, these data suggest that a certain initial threshold of PKC activation is required for induction of a differentiated monocytic phenotype while beyond this threshold, a growth-arrested and differentiated state in these human leukemic cells can be maintained regardless of TPA concentrations.

Cell Differentiation↗
PubMed1997

Lack of butyrate is associated with induction of Bax and subsequent apoptosis in the proximal colon of guinea pig.

BACKGROUND & AIMS: Butyrate stimulates proliferation and suppresses differentiation in normal colonic epithelial cells. Because the involved intracellular signaling mechanisms are unclear, this study investigated certain molecular effects of butyrate. METHODS: Tissue sheets from guinea pig proximal colon were incubated in Ussing chambers in the presence and absence of butyrate. Colonic tissues were examined by scanning and transmission electron microscopy, DNA laddering, Western blots, and immunohistochemistry. RESULTS: After incubation of the colonic mucosa for 150 minutes without butyrate, morphological studies showed massive apoptosis of colonocytes. Simultaneously, these colonocytes exhibited a significant oligonucleosomal DNA fragmentation. In contrast, addition of physiological concentrations of butyrate (10 mmol/L) to colonic sheets showed no detectable DNA fragmentation within 150 minutes. Western blot analysis showed little if any difference in the level of Bcl-2 expression in colonocytes incubated with or without butyrate up to 150 minutes. In contrast, expression of Bax proteins continuously increased after 45 minutes without butyrate and reached a fivefold induction after 150 minutes compared with cells incubated in the presence of butyrate. Moreover, immunohistochemistry using an anti-Bax antibody system showed enhanced labeling of the epithelial colonocytes in the absence of butyrate. CONCLUSIONS: Removal of butyrate induces increased expression of Bax proteins paralleled by rapid apoptosis of colonocytes in vitro.

Animals↗
PubMed1996

Specific determination of tyrosine-phosphorylated proteins and peptides by differential iodination.

A new method for the selective and quantitative determination of phosphotyrosine residues is presented using a differential iodination technique. Characterization of tyrosine-phosphorylated proteins was performed in a biological system using human U937 myeloid leukemia cells. The method is based on the saturation of free iodine binding sites using non-radioactive iodine. Samples are then treated with alkaline phosphatase. New iodine binding sites in dephosphorylated tyrosines are subsequently radio-iodinated, resulting in specific labeling of tyrosine phosphates. Separation is performed by RP-HPLC or sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Radiolabeled proteins are then identified using a radioactivity detector or autoradiography.

Alkaline Phosphatase↗
PubMed1996

Withdrawal of butyrate from the colonic mucosa triggers "mass apoptosis" primarily in the G0/G1 phase of the cell cycle.

Butyrate exerts a trophic effect on the colonocytes and plays a protective role in ulcerative colitis. In the present study, we investigated the effect of butyrate withdrawal on the colonic mucosa of the guinea-pig. The samples were mounted in Ussing chambers and bathed for 45, 60, 90 and 150 min with standard Ringer solution with or without sodium butyrate. Light and electron microscopy for morphology, electrophysiological methods for testing tissue function, histochemistry using the TUNEL method for localization of apoptotic cells and flow cytometry for cell cycle analysis were applied. Morphological observations revealed that butyrate deprivation caused a time-dependent hypoplasia and a rapid triggering of massive apoptosis as substantiated by the TUNEL assay. The epithelium, however, did not show discontinuities at any time. Electrophysiological data confirmed that no leakage of the epithelium had occurred. In the control specimens, the mucosa underwent a moderate reduction in height; apoptotic epithelial cells were infrequently observed. Cell cycle analysis of colonocytes isolated from the mucosa deprived of butyrate revealed a decrease in the percentage of cells occupying each phase of the cycle, especially the G0/G1 phase. Thus, in the absence of butyrate, apoptosis was enhanced and cell renewal reduced. The trophic protective action exerted by butyrate in both physiological and pathological conditions could derive from its capacity to modulate survival and death of colonocytes.

Animals↗
PubMed1995

Differential expression of c-myc, max and mxi1 in human myeloid leukemia cells during retrodifferentiation and cell death.

Previous studies in human myeloid leukemia cells (HL-60, U-937, THP-1) suggested an involvement of the c-myc gene in the control of mutually exclusive pathways, such as retrodifferentiation and cell death. Treatment of U-937 cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) which is associated with the induction of a monocytic differentiation program and growth arrest, revealed an initial up-regulation of c-myc, c-max, and mxi1 mRNAs after 1-6 h. Thereafter expression of these genes significantly declined to barely detectable levels when the cells ceased to grow after 12-24 h of TPA treatment. Between 7 and 11 days of TPA-induced G0/G1 cell cycle arrest, expression of the c-max and mxi1 genes continuously increased up to 8-fold until 32 days and declined to control levels when the cells regained proliferative capacity by 36 days. In contrast, c-myc mRNAs remained down-regulated during periods of growth arrest and increased only during re-entry into the cell cycle after 36 days. This effect is consistent with a retrodifferentiation process, whereby previously differentiated cells revert back to the undifferentiated phenotype and re-enter the cell cycle. Different results were obtained during serum starvation-induced cell death of U-937 cells. After 48-72 h of serum-starvation, expression of the c-myc and c-max genes were significantly down-regulated by 4-fold and 3-fold, respectively, while there was little, if any, change in mxi1 mRNA levels. Analysis of cell death in serum-starved U-937 cells demonstrated progressively increasing DNA fragmentation reaching 45.4% +/- 0.9% after 72 h. Synchronization of proliferating U-937 cells throughout distinct phases of the cell cycle exhibited little, if any, change in c-myc, c-max and mxi1 mRNAs. Furthermore, like c-myc, c-max and mxi1 mRNA transcripts appeared to be regulated primarily by post-transcriptional mechanisms, and c-max and mxi1 half-lives exceeded 4 h in contrast to < 60 min for the c-myc gene. Taken together, these findings suggested differential regulation and inverse expression levels of c-myc compared to c-max and mxi1 during differentiation, retrodifferentiation and cell death.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1994

Retrodifferentiation and cell death.

The reversibility of a differentiation program termed dedifferentiation, redifferentiation, or retrodifferentiation opens a spectrum of new possibilities for cellular development. During differentiation and retrodifferentiation, the expression of gene products associated with a differentiated phenotype and cell cycle regulation demonstrate inverse patterns. This effect requires a coordinated network that simultaneously controls cell growth and differentiation. In particular, crosstalk between induction of differentiation and G0/G1 cell cycle exit can be initiated and sustained by activated serine/threonine kinases and tyrosine kinases. Phosphorylation signals are relayed to certain genes or transcription factors such as Fos/Jun, EGR-1, NF-kappa B, MyoD, or the Myc/Max gene family. However, the precise regulation of these transcription factors to confer signals to differentiation-associated and cell cycle-regulatory genes remains unclear. Cell cycle exit into a transient G0'-arrest cycle or a terminal G0 phase is determined by a network of phosphorylation signals involving the retinoblastoma protein and a variety of factors such as the E2F family, cyclins, and cyclin-dependent kinases. In this context, a variety of differentiation-induced cell lines, including monocytic, neuronal, or muscle cells, can progress through the G0'-arrest cycle, whereby a certain population retains the capacity to retrodifferentiate and reenter the cell cycle. In contrast, the rest of the differentiated population enters the irreversible G0 phase (terminal commitment) that finally results in programmed cell death. The expression of growth arrest-specific (gas and gadd) genes is associated with the G0'-arrest cycle, and other factors, including c-myc, p53, mdm2, and bcl2/bclx, contribute to the regulation of the cell death program. Although the precise signaling cascade determining retrodifferentiation or cell death remains unclear, a coordinated inter- and intracellular regulation could establish a certain biological balance between these exclusive pathways. Consequently, a retrodifferentiation process may provide a potential for cell type conversion or transdifferentiation, whereby retrodifferentiated cells can be induced to develop via a different pathway according to tissue-specific requirements.

Animals↗
PubMed1994

Characterization of human TUR leukemia cells: continued cell cycle progression in the presence of phorbol ester is associated with resistance to apoptosis.

Human TUR leukemia cells were generated as a subclone of U937 monoblastoid leukemia cells. There was no obvious difference in the ultrastructure of both cell lines. Like in U937 cells, the expression of monocyte-specific surface markers such as CD14 was negligible in TUR cells. U937 cells and other human myeloid leukemia cell lines (HL-60, THP-1) can be induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to differentiate along the monocytic pathway. In contrast, exposure to TPA had no effect on the induction of the differentiation program in TUR cells. Thus, the presence of leukocyte integrins including CD11 and CD18, which are significantly induced during TPA-induced differentiation of HL-60, U937 and THP-1 cells, remained nearly unchanged at low levels in both TUR and TPA-treated TUR cells. Furthermore, while expression of major histocompatibility complex (MHC) class II antigens on U937 and TPA-treated U937 cells is barely detectable, there was a significantly constitutive expression of MHC class II, particularly human lymphocyte antigen (HLA-DR) on the surface of TUR and TPA-treated TUR cells. Exposure of human myeloid leukemia cells to TPA is also associated with growth arrest resulting either in a retrodifferentiation process or in programmed cell death. In contrast, TUR cells continued to proliferate in the presence of TPA although the proliferative capacity was continuously reduced by increasing concentrations of TPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoptosis↗