Induction of urothelial proliferation in rats by aristolochic acid through cell cycle progression via activation of cyclin D1/cdk4 and cyclin E/cdk2

2006 ◽  
Vol 44 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Horng-Rong Chang ◽  
Jong-Da Lian ◽  
Chia-Wen Lo ◽  
Yun-Ching Chang ◽  
Mon-Yuan Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Aristolochic Acid ◽  
Cyclin E ◽  
Cycle Progression

scholarly journals Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1.

1997 ◽  
Vol 17 (9) ◽  
pp. 5598-5611 ◽  
Author(s):  
D Woods ◽  
D Parry ◽  
H Cherwinski ◽  
E Bosch ◽  
E Lees ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
G1 Arrest ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Primary Mouse

The Raf family of protein kinases display differences in their abilities to promote the entry of quiescent NIH 3T3 cells into the S phase of the cell cycle. Although conditional activation of deltaA-Raf:ER promoted cell cycle progression, activation of deltaRaf-1:ER and deltaB-Raf:ER elicited a G1 arrest that was not overcome by exogenously added growth factors. Activation of all three deltaRaf:ER kinases led to elevated expression of cyclin D1 and cyclin E and reduced expression of p27Kip1. However, activation of deltaB-Raf:ER and deltaRaf-1:ER induced the expression of p21Cip1, whereas activation of deltaA-Raf:ER did not. A catalytically potentiated form of deltaA-Raf:ER, generated by point mutation, strongly induced p21Cip1 expression and elicited cell cycle arrest similarly to deltaB-Raf:ER and deltaRaf-1:ER. These data suggested that the strength and duration of signaling by Raf kinases might influence the biological outcome of activation of this pathway. By titration of deltaB-Raf:ER activity we demonstrated that low levels of Raf activity led to activation of cyclin D1-cdk4 and cyclin E-cdk2 complexes and to cell cycle progression whereas higher Raf activity elicited cell cycle arrest correlating with p21Cip1 induction and inhibition of cyclin-cdk activity. Using green fluorescent protein-tagged forms of deltaRaf-1:ER in primary mouse embryo fibroblasts (MEFs) we demonstrated that p21Cip1 was induced by Raf in a p53-independent manner, leading to cell cycle arrest. By contrast, activation of Raf in p21Cip1(-/-) MEFs led to a robust mitogenic response that was similar to that observed in response to platelet-derived growth factor. These data indicate that, depending on the level of kinase activity, Raf can elicit either cell cycle progression or cell cycle arrest in mouse fibroblasts. The ability of Raf to elicit cell cycle arrest is strongly associated with its ability to induce the expression of the cyclin-dependent kinase inhibitor p21Cip1 in a manner that bears analogy to alpha-factor arrest in Saccharomyces cerevisiae. These data are consistent with a role for Raf kinases in both proliferation and differentiation of mammalian cells.

scholarly journals Ectopic expression of cyclin D1 but not cyclin E induces anchorage-independent cell cycle progression.

1997 ◽  
Vol 17 (9) ◽  
pp. 5640-5647 ◽  
Author(s):  
D Resnitzky
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Cyclin E ◽  
Ectopic Expression ◽  
S Phase ◽  
G1 Arrest ◽  
Independent Manner ◽  
Cycle Progression

Normal fibroblasts are dependent on adhesion to a substrate for cell cycle progression. Adhesion-deprived Rat1 cells arrest in the G1 phase of the cell cycle, with low cyclin E-dependent kinase activity, low levels of cyclin D1 protein, and high levels of the cyclin-dependent kinase inhibitor p27kip1. To understand the signal transduction pathway underlying adhesion-dependent growth, it is important to know whether prevention of any one of these down-regulation events under conditions of adhesion deprivation is sufficient to prevent the G1 arrest. To that end, sublines of Rat1 fibroblasts capable of expressing cyclin E, cyclin D1, or both in an inducible manner were used. Ectopic expression of cyclin D1 was sufficient to allow cells to enter S phase in an adhesion-independent manner. In contrast, cells expressing exogenous cyclin E at a level high enough to overcome the p27kip1-imposed inhibition of cyclin E-dependent kinase activity still arrested in G1 when deprived of adhesion. Moreover, expression of both cyclins D1 and E in the same cells did not confer any additional growth advantage upon adhesion deprivation compared to the expression of cyclin D1 alone. Exogenously expressed cyclin D1 was down-regulated under conditions of adhesion deprivation, despite the fact that it was expressed from a heterologous promoter. The ability of cyclin D1-induced cells to enter S phase in an adhesion-independent manner disappears as soon as cyclin D1 proteins disappear. These results suggest that adhesion-dependent cell cycle progression is mediated through cyclin D1, at least in Rat1 fibroblasts.

scholarly journals Mechanisms of Cyclin-Dependent Kinase Inactivation by Progestins

1998 ◽  
Vol 18 (4) ◽  
pp. 1812-1825 ◽  
Author(s):  
Elizabeth A. Musgrove ◽  
Alexander Swarbrick ◽  
Christine S. L. Lee ◽  
Ann L. Cornish ◽  
Robert L. Sutherland
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cyclin D3 ◽  
Cdk Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Progestin Treatment

ABSTRACT The steroid hormone progesterone regulates proliferation and differentiation in the mammary gland and uterus by cell cycle phase-specific actions. In breast cancer cells the predominant effect of synthetic progestins is long-term growth inhibition and arrest in G1 phase. Progestin-mediated growth arrest of T-47D breast cancer cells was preceded by inhibition of cyclin D1-Cdk4, cyclin D3-Cdk4, and cyclin E-Cdk2 kinase activities in vitro and reduced phosphorylation of pRB and p107. This was accompanied by decreases in the expression of cyclins D1, D3, and E, decreased abundance of cyclin D1- and cyclin D3-Cdk4 complexes, increased association of the cyclin-dependent kinase (CDK) inhibitor p27 with the remaining Cdk4 complexes, and changes in the molecular masses and compositions of cyclin E complexes. In control cells cyclin E eluted from Superdex 200 as two peaks of ∼120 and ∼200 kDa, with the 120-kDa peak displaying greater cyclin E-associated kinase activity. Following progestin treatment, almost all of the cyclin E was in the 200-kDa, low-activity form, which was associated with the CDK inhibitors p21 and p27; this change preceded the inhibition of cell cycle progression. These data suggest preferential formation of this higher-molecular-weight, CDK inhibitor-bound form and a reduced number of cyclin E-Cdk2 complexes as mechanisms for the decreased cyclin E-associated kinase activity following progestin treatment. Ectopic expression of cyclin D1 in progestin-inhibited cells led to the reappearance of the 120-kDa active form of cyclin E-Cdk2 preceding the resumption of cell cycle progression. Thus, decreased cyclin expression and consequent increased CDK inhibitor association are likely to mediate the decreases in CDK activity accompanying progestin-mediated growth inhibition.

Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E

2005 ◽  
Vol 12 (Supplement_1) ◽  
pp. S47-S59 ◽  
Author(s):  
Alison J Butt ◽  
Catriona M McNeil ◽  
Elizabeth A Musgrove ◽  
Robert L Sutherland
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Endocrine Resistance ◽  
Cycle Progression ◽  
Er Positive ◽  
Oestrogen Signalling

Antioestrogen therapy is a highly effective treatment for patients with oestrogen-receptor (ER)-positive breast cancer, emphasising the central role of oestrogen action in the development and progression of this disease. However, effective antioestrogen treatment is often compromised by acquired endocrine resistance, prompting the need for a greater understanding of the down-stream mediators of oestrogen action that may contribute to this effect. Recent studies have demonstrated a critical link between oestrogen’s mitogenic effects and cell cycle progression, particularly at the G1 to S transition where key effectors of oestrogen action are c-Myc and cyclin D1, which converge on the activation of cyclin E-cdk2. These components are rapidly upregulated in response to oestrogen, and can mimic its actions on cell cycle progression, including re-initiating cell proliferation in antioestrogen-arrested cells. Here we review the roles of c-Myc, cyclin D1 and cyclin E in oestrogen action and endocrine resistance, and identify their potential as markers of disease progression and endocrine responsiveness, and as novel therapeutic targets in endocrine-resistant breast cancer.

Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells.

2003 ◽  
pp. 179-186 ◽  
Author(s):  
S F Doisneau-Sixou ◽  
C M Sergio ◽  
J S Carroll ◽  
R Hui ◽  
E A Musgrove ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Estrogen Regulation ◽  
Cycle Progression ◽  
P21 Waf1 ◽  
Regulation Of Cell Cycle ◽  
And Function

The central involvement of estrogen in the development of the mammary gland and in the genesis of breast cancer has lent impetus to studies of the links between estrogen action and the cell cycle machinery. Recent studies of the estrogenic regulation of molecules with known roles in the control of G1/S phase progression have resulted in significant advances in understanding these links. Estrogens independently regulate the expression and function of c-Myc and cyclin D1 and the induction of either c-Myc or cyclin D1 is sufficient to recapitulate the effects of estrogen on cell cycle progression. These pathways converge at the activation of cyclin E-Cdk2 complexes. The active cyclin E-Cdk2 complexes are depleted of the cyclin dependent kinase (CDK) inhibitor p21(WAF1/CIP1) because of estrogen-mediated inhibition of nascent p21(WAF1/CIP1). Insulin and estrogen synergistically stimulate cell cycle progression, and the ability of estrogen to antagonize an insulin-induced increase in p21(WAF1/CIP1) gene expression appears to underlie this effect. Antiestrogen treatment of MCF-7 cells leads to an acute decrease of c-Myc expression, a subsequent decline in cyclin D1, and ultimately arrest of cells in a state with features characteristic of quiescence. An antisense-mediated decrease in c-Myc expression results in decreased cyclin D1 expression and inhibition of DNA synthesis, mimicking the effects of antiestrogen treatment and emphasizing the importance of c-Myc as an estrogen/antiestrogen target. These data identify c-Myc, cyclin D1, p21(WAF1/CIP1) and cyclin E-Cdk2 as central components of estrogen regulation of cell cycle progression and hence as potential downstream targets that contribute to the role of estrogen in oncogenesis.

scholarly journals PARP14 regulates cyclin D1 expression to promote cell-cycle progression

Oncogene ◽  
2021 ◽  
Author(s):  
Michael J. O’Connor ◽  
Tanay Thakar ◽  
Claudia M. Nicolae ◽  
George-Lucian Moldovan
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Promote Cell Cycle Progression

A Novel Function for Cyclin E in Cell Cycle Progression

2007 ◽  
pp. 31-39
Author(s):  
Yan Geng ◽  
Youngmi Lee ◽  
Markus Welcker ◽  
Jherek Swanger ◽  
Agnieszka Zagozdzon ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression

scholarly journals FTO Demethylates Cyclin D1 mRNA and Controls Cell-Cycle Progression

Cell Reports ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 107464 ◽  
Author(s):  
Mayumi Hirayama ◽  
Fan-Yan Wei ◽  
Takeshi Chujo ◽  
Shinya Oki ◽  
Maya Yakita ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Cycle Progression
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