SEARCH · PubMed Health

Results for “cellular proliferation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

PubMed2002

Androgen receptor expression and cellular proliferation during transition from androgen-dependent to recurrent growth after castration in the CWR22 prostate cancer xenograft.

Androgen receptor expression was analyzed in the CWR22 human prostate cancer xenograft model to better understand its role in prostate cancer recurrence after castration. In androgen-dependent tumors, 98.5% of tumor cell nuclei expressed androgen receptor with a mean optical density of 0.26 +/- 0.01. On day 2 after castration androgen deprivation decreased immunostained cells to 2% that stained weakly (mean optical density, 0.16 +/- 0.08). Cellular proliferation measured using Ki-67 revealed <1% immunostained cells on day 6. Androgen receptor immunostained cells increased to 63% on day 6 and 84% on day 32 although immunostaining remained weak. Cellular proliferation was undetectable beyond day 6 after castration until multiple foci of 5 to 20 proliferating cells became apparent on day 120. These foci expressed increased levels of prostate-specific antigen, an androgen receptor-regulated gene product. In tumors recurrent 150 days after castration androgen receptor-immunostaining intensity was similar to CWR22 tumors from intact mice although the percentage of cells immunostained was more variable. The appearance of proliferating tumor cells that expressed androgen receptor and prostate-specific antigen 120 days after castration suggests that these cells represent the origin of recurrent tumors.

Androgens↗

PubMed1993

[Study on the cellular proliferation and endocrine activity of the parathyroid gland in hyperparathyroidism].

Flow cytometric DNA analysis was performed in 21 cases of primary hyperparathyroidism (19 adenomas in 19 cases and 5 glands with primary hyperplasia) and 24 glands with secondary hyperplasia. Tissue intact-PTH concentration was measured in another 41 glands with secondary hyperplasia. Glands with adenoma had a higher proliferative index than normal glands or glands with secondary hyperplasia. In the adenoma group, there was a negative correlation between proliferative index and age, an indicator of the tumorous nature of adenomas. Daily urinary calcium excretion in case of adenoma and tissue intact-PHT concentration in glands with secondary hyperplasia also showed correlations with proliferative index, which demonstrates a close relationship between cellular proliferation and endocrine activity. Gland weight and proliferative index had no significant correlation in both groups. Therefore, another mechanism besides cellular proliferation and endocrine activity, such as number of non-functional parathyroid cells, should be considered.

Adenoma↗

PubMed1997

Cellular kinetics in Barrett's epithelium carcinogenic sequence: roles of apoptosis, bcl-2 protein, and cellular proliferation.

To gain insight into the neoplastic progression of Barrett's epithelium (BE), we assessed the expression of Ki-67 antigen and bcl-2 protein and the occurrence of apoptosis in metaplastic epithelium with and without regenerative atypia (RA), low-grade dysplasia, and high-grade dysplasia (HGD). To refine our understanding of the epithelial kinetics during the carcinogenic sequence, we performed separate analyses of four different mucosal regions, i.e., surface epithelium, upper and lower crypts, and glands. Expansion of the proliferative zone was noted in dysplasia and to a mild degree in epithelium with RA but not in BE. Expression of bcl-2 protein was seen in the proliferative zone in BE and showed a significant increase in RA but was essentially absent in HGD. Numerous apoptotic nuclei were seen in HGD, decreasing along the cellular gradient from gland to surface. We noted a positive correlation between Ki-67 and bcl-2 in the proliferative zone of BE and RA, whereas a negative correlation was present on the surface of RA. Ki-67 was positively correlated with apoptosis in the lower crypts of HGD. bcl-2 expression was negatively correlated with apoptosis in all regions except the proliferative zone of dysplastic areas. Our findings suggest that overexpression of bcl-2 protein is not an important step in the carcinogenesis of BE. We confirm the upward shift of cellular proliferation in dysplastic epithelia. Apoptosis that is increased in dysplasia might play a significant role in carcinogenesis by restraining increased cellular proliferation.

Adenocarcinoma↗

PubMed1982

The effect of altered luminal nutrition on cellular proliferation and plasma concentrations of enteroglucagon and gastrin after small bowel resection in the rat.

Luminal nutrition is known to have a trophic effect on small bowel mucosa after intestinal resection. Humoral agents, however, may also contribute to this process. Two of the proposed humoral agents, enteroglucagon and gastrin, were therefore investigated after intestinal resection and transection in the rat, and changes in their concentration in the plasma were related to cellular proliferation. Forty-eight male Wistar rats had either 75 per cent proximal small bowel resection or jejunal transection. The animals were further divided into three groups, each with a different nutritional intake. The first group were allowed food ad libitum. The second group were kept under hypothermic conditions which resulted in hyperphagia, while the last group were nourished intravenously. A further 8 animals had a laparotomy only (sham operation). All animals were killed 12 days after operation, plasma enteroglucagon and gastrin were measured, while determination of the crypt cell production rate (CCPR) was used to denote cellular proliferation. In each group resected rats had significantly higher crypt cell production rates and greater enteroglucagon levels compared with transected animals. However, only in the normally fed group was plasma gastrin increased in resected animals, there being no significant difference in the plasma concentration of this peptide in transected compared with resected rats, in both the intravenously fed and hyperphagic groups. In the models studied enteroglucagon appears to be a more likely candidate for a humoral trophic agent than gastrin in intestinal adaptation.

Adaptation, Physiological↗

PubMed1997

Brca2 is required for embryonic cellular proliferation in the mouse.

Mutations of the tumor suppressor gene BRCA2 are associated with predisposition to breast and other cancers. Homozygous mutant mice in which exons 10 and 11 of the Brca2 gene were deleted by gene targeting (Brca2(10-11)) die before day 9.5 of embryogenesis. Mutant phenotypes range from severely developmentally retarded embryos that do not gastrulate to embryos with reduced size that make mesoderm and survive until 8.5 days of development. Although apoptosis is normal, cellular proliferation is impaired in Brca2(10-11) mutants, both in vivo and in vitro. In addition, the expression of the cyclin-dependent kinase inhibitor p21 is increased. Thus, Brca2(10-11) mutants are similar in phenotype to Brca1(5-6) mutants but less severely affected. Expression of either of these two genes was unaffected in mutant embryos of the other. This study shows that Brca2, like Brca1, is required for cellular proliferation during embryogenesis. The similarity in phenotype between Brca1 and Brca2 mutants suggests that these genes may have cooperative roles or convergent functions during embryogenesis.

Animals↗

PubMed2000

Differential impact of nicotine on cellular proliferation and cytokine production by LPS-stimulated murine splenocytes.

The immunoregulatory effects of nicotine have not been fully clarified and the reported data are often conflicting. The present study investigated the role of nicotine as an immunomodulator of murine splenocytes stimulated by lipopolysaccharide (LPS), the endotoxin component of gram-negative bacteria. BALB/c female mice of two different ages, young (2-3 months) and old (18-22 months), were used. The cells were incubated with nicotine at two different time points, 3 h pre-incubation and concurrent incubation relevant to LPS stimulation, before further incubation for 48 or 72 h. Treatment of murine splenocytes with nicotine showed an impact on cellular proliferation as well as on the production of the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The results indicated that nicotine significantly inhibited cellular proliferation of murine splenocytes in a concentration-related manner (32, 64 and 128 microg/ml). Timing of nicotine exposure prior to LPS stimulation was critical in terms of immunological impact on cytokine production. TNF-alpha and IL-6 production were significantly enhanced by 1 microg/ml of nicotine when cells were pre-incubated with nicotine for 3 h compared to concurrent incubation relative to LPS stimulation. The alteration in cytokine production varied with the age of the mouse. TNF-alpha production was significantly inhibited by nicotine in young mice, while IL-6 production was significantly inhibited by nicotine in old mice. Since any immunomodulation that alters the profile of these cytokines may cause an imbalance in the immune system impinging on health status, these findings may be important when dealing with the concept of nicotine as a therapeutic agent.

Animals↗

PubMed2004

Does administration of isosorbide mononitrate affect cellular proliferation in oral squamous cell carcinoma? A prospective randomized clinical study.

PURPOSE: There has been much interest in the role that the signaling molecule nitric oxide (NO) plays in cancer. NO has both tumor-promoting and tumor-inhibiting effects that are dependent on its local tissue concentration. In animal studies, the administration of exogenous NO has reduced both tumor growth and dissemination, and in vitro NO administration causes death of oral cancer cell lines. We evaluated the oral administration of the NO donor drug isosorbide mononitrate (ISMO) on cellular proliferation in patients with oral squamous cell carcinoma. MATERIALS AND METHODS: A prospective randomized double-blind study was performed on 31 patients with biopsy-confirmed oral squamous cell carcinoma. Following incisional biopsy, patients were randomized to receive either ISMO (at a dose of 20 mg twice a day) or placebo tablets for 2 weeks before definitive resection. Cellular proliferation was compared between biopsy and resection specimens, using the immunohistochemical marker Ki-67. RESULTS: No statistical difference was found between Ki-67 indices in initial biopsy and resection specimens after ISMO (P =.23) or placebo (P =.5) administration. There were no obvious clinical changes seen in the tumor during the clinical trial as a result of ISMO administration. CONCLUSION: Although high concentrations of NO are cytotoxic, it is unlikely that administration of NO at an increased dose would be useful in the management of oral cancer because this would result in unacceptable systemic side effects. The possible manipulation of NO in oral cancer is discussed.

Adult↗

PubMed1998

Activin regulates betaA-subunit and activin receptor messenger ribonucleic acid and cellular proliferation in activin-responsive testicular tumor cells.

Activin, a member of the transforming growth factor-beta superfamily of growth and differentiation factors, has a number of actions in embryonic as well as adult tissues. These actions are mediated via a family of receptors containing two subtypes and at least two members of each subtype. Recent evidence demonstrates that activin-responsive cell lines containing different subsets of these receptors are valuable models for dissecting functional relationships among receptor subtype, signal transduced, and response obtained. TT cells, derived from a p53(-/-)/alpha-inhibin(-/-) mouse testicular tumor, respond to activin by proliferating, a response that can be inhibited by follistatin (FS) treatment. Using semiquantitative RT-PCR methods, we characterized steady state messenger RNA (mRNA) levels for the inhibin/activin subunits, FS, and activin receptor subtypes under basal conditions and in the presence of activin or FS. These cells produced ample immunoreactive activin A and FS, necessitating higher treatment doses to observe any modulation of cellular proliferation. Furthermore, in the presence of exogenous activin, mRNA levels for activin receptor type IIA (ACTRIIA) and betaA were significantly and profoundly suppressed. In addition, both ACTR1B and ACTRIIB were detectable and down-regulated by exogenous activin, although not to the degree observed for ACTRIIA and betaA. Finally, activin treatment at the higher doses, which decreased activin receptor mRNA levels, resulted in inhibition of cellular proliferation. Taken together with previous observations, our results support the model that these tumor cells respond to an autocrine activin signal by proliferating, whereas exogenous or excess activin results in down-regulation of activin receptor and activin biosynthesis, suggesting a potential autocrine/paracrine mechanism by which activin can modulate its own signal.

Activin Receptors↗

PubMed2000

Allelic imbalance on 16q in small, unifocal hepatocellular carcinoma: correlation with HBV and HCV infections and cellular proliferation rate.

In advanced hepatocellular carcinoma (HCC), allelic loss on chromosome 16q may occur. To better define the frequency of this alteration in small HCC and to more closely identify the affected region for further positional cloning of the putative tumor suppressor gene contained in this region, microsatellite polymorphism analysis was conducted on small, unifocal HCC, without signs of intrahepatic or systemic spread. We also tried to assess its possible correlation with hepatitis virus infections (HBV and HCV) and cellular proliferation rate. DNA from 35 small (<4 cm), unifocal HCC and from the corresponding nontumorous surrounding tissue was analyzed by 10 sets of microsatellite polymorphic markers. Serologic markers for hepatitis virus B and C infections were investigated in all cases. AgNOR protein quantity was assessed by image analysis on cryostatic sections stained with silver. The percentage of tumours with allelic imbalance ranged from 11.1 to 37%. The minimal involved region was assessed at 16q24.3, corresponding to the D16S413 marker, which was also the most commonly affected locus (10 of 27 informative cases, 37%). Allelic imbalance on chromosome 16q was significantly associated with HBV infection: 8 of 10 cases showed an actual or previous HBV infection in the group showing allelic imbalance, versus 6 with a previous HBV infection out of 25 in the control group (P < 0.01). No difference was found as far as HCV infection is concerned. The mean (+/-SE) AgNOR protein value in six cases showing allelic imbalance was 8.36 +/- 1.2 microm2, compared to 6.45 +/- 0.68 microm2 in 13 cases retaining both the alleles at 16q but the difference proved not statistically significant. In conclusion, in this series of small, unifocal HCC the minimal region of allelic imbalance on 16q was restricted to 16q24.3. It was found to be associated with HBV infection but not with increased cellular proliferation rate.

Aged↗

PubMed1978

Patterns of cellular proliferation during thyroid organogenesis.

The changes in rate and location of cellular proliferation were analyzed to determine if localized areas of cell division were influencing shape changes in the chick thyroid. Pulse labeling with tritiated thymidine indicates that the gland's labeling index declines throughout its development. Initially, the thyroid placode has a lower labeling index than the neighboring pharyngeal epithelium. An evaluation of the positions of pulse-labeled cells reveals that the evaginating thyroid grows by annexing cells from the pharyngeal epithelium. The older evaginated regions of the gland exhibit the lowest labeling indices. The newly acquired regions still maintain higher labeling indices.

Animals↗

PubMed1995

Inhibition of cellular proliferation by the Wilms' tumor suppressor WT1 is associated with suppression of insulin-like growth factor I receptor gene expression.

We have investigated the regulation of the insulin-like growth factor I receptor (IGF-I-R) gene promoter by the Wilms' tumor suppressor WT1 in intact cells. The levels of endogenous IGF-I-R mRNA and the activity of IGF-I-R gene promoter fragments in luciferase reporter constructs were found to be significantly higher in G401 cells (a Wilms' tumor-derived cell line lacking detectable WT1 mRNA) than in 293 cells (a human embryonic kidney cell line which expresses significant levels of WT1 mRNA). To study whether WT1 could suppress the expression of the endogenous IGF-I-R gene, WT1-negative G401 cells were stably transfected with a WT1 expression vector. Expression of WT1 mRNA in G401 cells resulted in a significant decrease in the rate of cellular proliferation, which was associated with a reduction in the levels of IGF-I-R mRNA, promoter activity, and ligand binding and with a reduction in IGF-I-stimulated cellular proliferation, thymidine incorporation, and anchorage-independent growth. These data suggest that a major aspect of the action of the WT1 tumor suppressor is the repression of IGF-I-R gene expression.

Cell Division↗

PubMedDate not supplied

Cellular proliferation and ploidy of the gastric mucosa: the role of Helicobacter pylori.

BACKGROUND/AIMS: Recently, H. pylori has been recognized as a risk factor for gastric adenocarcinoma. As such, we have analyzed the DNA content of gastric epithelial cells in an attempt to reveal the role of H. pylori in gastric carcinogenesis. METHODOLOGY: Fifty-three subjects presented with gastric dyspepsia, 39 males and 14 females, with a mean age of 42.15 (+/- 13.16) years. They were referred to the out-patient clinic to undergo endoscopic examination for the first time. Biopsy specimens from the antrum of each subject were subjected to culture for the presence of H. pylori histologic diagnosis, and DNA flow cytometry for the analysis of cellular proliferation and DNA policy. RESULTS: The endoscopic diagnoses were normal appearance (12), Gastric ulcer (12), duodenal ulcer (29). Thirty-eight (72%) subjects were positive, and 15 (28%) subjects were negative for H. pylori. Abnormal DNA-content (aneuploidy) was found in specimens from the antrums of 3 patients, 2 patients with duodenal ulcers (DU, and one with a gastric ulcer (GU). The cellular proliferation detected by flow cytometry in the form of proliferative index (PI; percentage of cells in the DNA S and G2M phases) was 27.88 (+/- 12.48) and 14.17 (+/-2.94) in the antrums of those positive and negative for H. pylori, respectively. A very significant increase in the PI (p < 0.005) was found between subjects positive and negative for H. pylori. Patients with DU and H pylori infection had the highest PI, and the PI was significantly higher than in patients with DU, but without infection. Regarding histology, there was a significant increase in the PI in the presence of H. pylori infection in either CAG or dysplasia groups as compared to cases without infection in the same groups. CONCLUSION: These results show that H. pylori infection is associated with changes in the DNA-content and cellular proliferative activity, suggesting that H. pylori may be implicated in gastric carcinogenesis. Also, the significant increase in the PI along the progression of severity of the disease suggests that measuring this parameter might allow more accurate monitoring of patients, so that a targeted therapeutic protocol may be defined.

Adult↗

PubMed1998

Extracellular calcium-sensing receptor in rat oligodendrocytes: expression and potential role in regulation of cellular proliferation and an outward K+ channel.

A G protein-coupled, extracellular calcium (Ca(0)2+)-sensing receptor (CaR) cloned from parathyroid, kidney, and brain plays crucial roles in systemic calcium metabolism. In brain, the CaR is located in nerve terminals as well as in fiber tracts, where it may be expressed in glia. Moreover, there is Ca2+- and K+-dependent communication between axons and oligodendroglia. To investigate further the potential role of the CaR in oligodendroglia, we studied expression of CaR mRNA and protein as well as the effects of CaR agonists on cellular proliferation and Ca2+-activated K+ channel activity in immature rat oligodendrocytes in primary culture. Reverse transcriptase polymerase chain reaction and sequencing of CaR transcripts from oligodendrocytes revealed >99% sequence identity with the rat kidney CaR. Northern analysis demonstrated 7.5 and 4.1 kb transcripts in oligodendrocytes, similar to those in rat parathyroid and kidney, while Western analysis and immunocytochemistry with CaR-specific antisera showed the presence of CaR protein. Immunocytochemically, the CaR was colocalized with galactocerebroside in the cultured oligodendrocytes. Raising Ca(0)2+ from 1.8 to 4.8 mM or addition of the polycationic CaR agonist neomycin (300 microM) modestly but significantly increased [3H]-thymidine incorporation into oligodendrocytes. Elevating Ca(0)2+ from 0.75 to 3.0 mM or addition of 100 microM neomycin also produced 2-2.5-fold increases in the open state probability (Po) of an outward K+ channel with a unitary conductance of 88+/-5 pS. Taken together, our data show that the CaR is expressed in immature oligodendrocytes and may be functionally linked to cellular proliferation and an outward K+ channel potentially contributing to local ionic homeostasis in the vicinity of oligodendroglia.

Animals↗

PubMed1999

Extracellular calcium-sensing receptor induces cellular proliferation and activation of a nonselective cation channel in U373 human astrocytoma cells.

A receptor for extracellular calcium ions (Ca2+o), cloned from parathyroid gland, serves a critical function in Ca2+o homeostasis by regulating PTH release via "sensing" of its physiological agonist, Ca2+o. Its cloning from rat striatum revealed that the extracellular calcium-sensing receptor (CaR) could be involved in sensing ambient Ca2+o within the brain, where Ca2+ plays key roles in virtually all aspects of central nervous system (CNS) function. The CaR is expressed in neurons, oligodendrocytes, microglia and the human astrocytoma cell line, U87 where its functions include control of cellular proliferation and modulation of ion channels, such as outward K+ channels and nonselective cation channels (NCC). In this report, we have shown that the CaR is expressed in U373 cells as assessed by RT-PCR using CaR-specific primers followed by sequencing of the amplified products, by Northern blot analysis using a CaR-specific probe as well as by Western analysis utilizing a specific polyclonal anti-CaR antiserum. Furthermore, agents known to activate the cloned CaR induce increases in cellular proliferation and the open probability of an NCC. Thus our study strongly suggests that elevated levels of Ca2+o, acting via the CaR, activate an NCC that could contribute to the associated CaR-induced stimulation of proliferation.

Animals↗

PubMed2005

The involvement of thioredoxin and thioredoxin binding protein-2 on cellular proliferation and aging process.

Recent reports on aging have revealed that many genetic loci affecting life span are closely linked to the machinery either producing or defending oxidative stress. Protective mechanisms against oxidative stress are thus important in countering the aging process. Thioredoxin (TRX) is a small thiol-mediated protein with a redox-active disulfide/dithiol within the conserved active site. TRX transgenic mice are more resistant than control mice to a variety of oxidative stresses including infection and inflammation. Moreover, we observed that the median life span of TRX tg mice was extended up to 135% compared to that of controls. TRX binding protein-2 (TBP-2), which is identical to vitamin D3 upregulated protein 1 (VDUP1), was identified as a binding molecule to TRX, and a negative regulator of TRX function. The expression of TBP-2/VDUP1 is frequently lost in tumor tissue and cell lines, and ectopic expression of TBP-2/VDUP1 suppresses cellular proliferation along with cell cycle arrest at the G1 phase. These findings suggest that TRX and TBP-2/VDUP1 are involved not only in cytoprotective functions against oxidative stress, but also in the regulation of cellular proliferation and the aging process.

Aging↗

PubMed2003

Influence of the neural tube/notochord complex on MyoD expression and cellular proliferation in chicken embryos.

Important advances have been made in understanding the genetic processes that control skeletal muscle formation. Studies conducted on quails detected a delay in the myogenic program of animals selected for high growth rates. These studies have led to the hypothesis that a delay in myogenesis would allow somitic cells to proliferate longer and consequently increase the number of embryonic myoblasts. To test this hypothesis, recently segmented somites and part of the unsegmented paraxial mesoderm were separated from the neural tube/notochord complex in HH12 chicken embryos. In situ hybridization and competitive RT-PCR revealed that MyoD transcripts, which are responsible for myoblast determination, were absent in somites separated from neural tube/notochord (1.06 and 0.06 10(-3) attomol MyoD/1 attomol beta-actin for control and separated somites, respectively; P<0.01). However, reapproximation of these structures allowed MyoD to be expressed in somites. Cellular proliferation was analyzed by immunohistochemical detection of incorporated BrdU, a thymidine analogue. A smaller but not significant (P = 0.27) number of proliferating cells was observed in somites that had been separated from neural tube/notochord (27 and 18 for control and separated somites, respectively). These results confirm the influence of the axial structures on MyoD activation but do not support the hypothesis that in the absence of MyoD transcripts the cellular proliferation would be maintained for a longer period of time.

Animals↗

PubMed1997

Adenovirus-mediated expression of the secreted form of basic fibroblast growth factor (FGF-2) induces cellular proliferation and angiogenesis in vivo.

Blood supply through collateral arteries is of critical importance in occlusive arterial diseases such as coronary atherosclerosis. Induction of angiogenic growth factor within either the narrowing arteries or jeopardized myocardium may promote angiogenesis in vivo, leading to salvage of ischemic myocardium. We constructed a replication-defective adenovirus (AdCAsFGF-2) coding for human basic fibroblast growth factor (FGF)-2 that is modified, so that its secretion will be facilitated, by tagging a signal sequence derived from FGF-4. A large quantity of FGF-2 was detected in both the cell lysate and culture medium of COS cells infected with AdCAsFGF-2, indicating that FGF-2 was secreted at least partly from the infected cells. The conditioned medium from the infected COS cells stimulated DNA synthesis in and induced cellular proliferation of arterial smooth muscle cells. These effects were eliminated by adenovirus-mediated overexpression of a dominant-negative truncated FGF-receptor type 1. Implantation of a gel of basement membrane proteins containing fibroblasts infected with AdCAsFGF-2 into the ventral subcutaneous space of mice induced extensive cellular proliferation and the formation of functional arterioles. Cells surrounding the vessels were positively immunostained with antibodies recognizing either smooth muscle-specific alpha-actin or factor VIII antigen as a marker for endothelium. These results suggest that AdCAsFGF-2 may be useful for delivering functional FGF-2 into tissues and may lead to therapeutic angiogenesis in vivo.

Actins↗

PubMed2005

RIalpha influences cellular proliferation in cancer cells by transporting RFC40 into the nucleus.

The regulatory subunit (RIalpha) of cAMP-dependent Protein Kinase A (PKA) is overexpressed in a variety of tumors and carcinomas such as renal cell carcinomas, pituitary tumors of the rat, malignant osteoblasts, colon carcinomas, serous ovarian tumors and primary human breast carcinomas. However, the direct relation between overexpression of RIalpha and malignancy is still unclear. We have recently identified a novel interaction between RIalpha and RFC40, the second subunit of Replication Factor C (RFC), and have demonstrated that this interaction may be associated with cell survival. Coincidentally, RFC40 is overexpressed in gestational trophoblastic diseases such as choriocarcinomas. This study was undertaken to investigate a possible functional role for both these proteins together, in DNA replication and cellular proliferation. In the course of this study, a nonconventional nuclear localization signal was identified for RIalpha. Nuclear transport of RFC40 was found to be dependent on RIalpha, and this transport appeared to be a crucial step for cell cycle progression from G1 to S phase. Impairment in the nuclear transport of RFC40 by RIalpha arrested cells in G1 phase. These findings provide evidence for a previously unknown mechanism for the nuclear transport of RFC40 and also for a novel mechanism for cellular proliferation.

Active Transport, Cell Nucleus↗