Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells

Stacey, Dennis W.

doi:10.1016/s0955-0674(03)00008-5

Cited by 415 publications

(313 citation statements)

References 17 publications

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“…Several studies conducted so far have assessed the deregulation of the pRb-pathway components in various human tumors and cell-lines, provided these pathway alterations play an obligatory role in tumorigenesis. The concomitant high level of p27 KIP1 is required for the assembly of active cyclin D1-CDK4 [45]. In the presence of ZOL in both cholangiocarcinoma cell lines a reduced expression of the inhibitor p27 Kip1 and a concomitant suppression of the cell cycle promoter D1 were observed.…”

Section: Discussionmentioning

confidence: 93%

“…In the presence of ZOL in both cholangiocarcinoma cell lines a reduced expression of the inhibitor p27 Kip1 and a concomitant suppression of the cell cycle promoter D1 were observed. The dual suppression of cyclin D1 and p27 KIP1 , two critical control molecules, and the persistence of pRb in the hyperphosphorylated status should allow the cells to freely enter in the S-phase and to accelerate through the cell cycle [45]. The dose-dependent accumulation of cells in the S-phase, however, suggests an arrest at the S-phase checkpoint.…”

Section: Discussionmentioning

confidence: 99%

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Zoledronic acid determines S-phase arrest but fails to induce apoptosis in cholangiocarcinoma cells

Romani

Desenzani

Morganti

et al. 2009

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In conclusion, our study indicates that zoledronic acid induces S-phase arrest and cell-narrowing, both reversed by GGOH and, by changing the delicate balance between pro-apoptotic and antiapoptotic proteins, allows survival of cholangiocarcinoma cells.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Zoledronic acid determines S-phase arrest but fails to induce apoptosis in cholangiocarcinoma cells

Romani

Desenzani

Morganti

et al. 2009

Biochemical Pharmacology

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“…In [48], the level of cyclin D is quantified during the cycle: the protein is multiplied by a factor taken between 2 and 5 during the G1 phase. We adjust the maximum level of cyclin D to reach a concentration five times higher than in the beginning of the G1 phase.…”

Section: Appendix a Determination Of The Parametersmentioning

confidence: 99%

A mathematical model of HiF-1-mediated response to hypoxia on the G1/S transition

Bedessem

Stéphanou

2014

Mathematical Biosciences

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Hypoxia is known to influence the cell cycle by increasing the G1 phase duration or by inducing a quiescent state (arrest of cell proliferation). This entry into quiescence is a mean for the cell to escape from hypoxia-induced apoptosis. It is suggested that some cancer cells have gain the advantage over normal cells to easily enter into quiescence when environmental conditions, such as oxygen pressure, are unfavorable [43,1]. This ability contributes in the appearance of highly resistant and aggressive tumor phenotypes [2].The HiF-1α factor is the key actor of the intracellular hypoxia pathway.As tumor cells undergo chronic hypoxic conditions, HiF-1α is present in higher level in cancer than in normal cells. Besides, it was shown that genetic mutations promoting overstabilization of HiF-1α are a feature of various types of cancers [8]. Finally, it is suggested that the intracellular level of HiF-1α can be related to the aggressiveness of the tumors [53,24,4,10] However, up to now, mathematical models describing the G1/S transition under hypoxia, did not take into account the HiF-1α factor in the hypoxia pathway.Therefore, we propose a mathematical model of the G1/S transition under hypoxia, which explicitly integrates the HiF-1α pathway. The model reproduces the slowing down of G1 phase under moderate hypoxia, and the entry into quiescence of proliferating cells under severe hypoxia. We show how the inhibition of cyclin D by HiF-1α can induce quiescence; this result provides a theoretical explanation to the experimental observations of Wen et al. (2010). Thus, our model confirms that hypoxia-induced chemoresistance can be linked, for a part, to the negative regulation of cyclin D by HiF-1α.

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“…Cytometric analysis of cyclin D1, EdU, and DNA staining (not shown) revealed that cyclin D1 expression in neural stem cells was cell cycle dependent, highest during G1 phase and lowest during S phase, as we observed in other cell types (Fig. 1C) (25)(26)(27). The expression of cyclin D1 was also tested following induction of differentiation in these neural stem cell cultures by growth factor removal for 2 weeks.…”

Section: Cyclin D1 Expression In Neural Cellsmentioning

confidence: 60%

“…On entry into G2 phase, the cessation of Thr 286 phosphorylation together with stabilization of cyclin D1 mRNA by positive growth conditions allows the re-elevation of cyclin D1 to high levels (23). This induction during G2 phase makes the cell competent to continue active cell cycle progression through the upcoming cell cycle (24)(25)(26)(27).…”

mentioning

confidence: 99%

The checkpoint kinase ATM protects against stress‐induced elevation of cyclin D1 and potential cell death in neurons

Hitomi

Stacey

2010

Cytometry Pt A

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Quantitative cytometric studies show that cyclin D1 levels must decline during S phase for proper cell cycle progression, and that cyclin D1 decline follows phosphorylation induced by the checkpoint kinases ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). ATM is mutated in ataxia telangiectasia (AT), a disease characterized by progressive neurodegeneration. Importantly, neurodegeneration in many cases has been linked to the increased expression of cyclin D1 in neurons leading to inappropriate cell cycle entry. These facts prompted us to test the possibility that ATM normally protects against neural degeneration by suppressing cyclin D1 levels, particularly following genotoxic stress. For this purpose, neural stem cells were induced to differentiate into mature neural cells, including neurons. ATM activity in these cultures was inhibited with a specific chemical inhibitor in the presence or absence of hydrogen peroxide treatment, and the effect on cyclin D1 expression was determined by quantitative, single cell cytometric analyses. As predicted, inhibition of ATM did promote elevation of cyclin D1 in differentiated neurons, particularly under conditions of oxidative stress. The survival of differentiated neurons and of neural stem cells was reduced by such treatments. These data support our suggestion that ATM functions to maintain low levels of cyclin D1 expression in differentiated neurons; and may provide important clues in understanding neural degeneration in general. ' 2010 International Society for Advancement of Cytometry

show abstract

Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells

Cited by 415 publications

References 17 publications

Zoledronic acid determines S-phase arrest but fails to induce apoptosis in cholangiocarcinoma cells

Zoledronic acid determines S-phase arrest but fails to induce apoptosis in cholangiocarcinoma cells

A mathematical model of HiF-1-mediated response to hypoxia on the G1/S transition

The checkpoint kinase ATM protects against stress‐induced elevation of cyclin D1 and potential cell death in neurons

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