Reversal of an antiestrogen-mediated cell cycle arrest of MCF-7 cells by viral tumor antigens requires the retinoblastoma protein-binding domain

Varma, Hemant; Conrad, Susan E.

doi:10.1038/sj.onc.1203827

Cited by 22 publications

(24 citation statements)

References 48 publications

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“…Essential to this is overexpression of G1/S cyclins, as is demonstrated in this study in which cell lines with a wild type pRb have been used. A similar effect has been reported for introduction of antisense p21 or p27 (Carroll et al, 2000;Cariou et al, 2000), and of a SV40 large T mutant that results in inactivation of pRb, leading to sustained E2F activity (Varma and Conrad, 2000). Translating these findings to the clinical situation, it is remarkable that overexpression of cylin A and absence of Rb expression in the primary breast cancer have been associated with failure to tamoxifen treatment in large series of breast cancer cases (Michalides et al, 2002;Anderson et al, 1996).…”

Section: Discussionmentioning

confidence: 68%

Involvement of G1/S cyclins in estrogen-independent proliferation of estrogen receptor-positive breast cancer cells

et al. 2002

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Estrogen receptor-mediated transcription is enhanced by overexpression of G1/S cyclins D1, E or A in the presence as well in the absence of estradiol. Excess of G1/S cyclins also prevents the inhibition of transactivation of estrogen receptor (ER) by the pure antiestrogen ICI 182780. Cyclin D1 mediates this transactivation independent of complex formation to its CDK4/6 partner. This raises the possibility that overexpression of G1/S cyclins renders growth of ER-positive breast cancer hormone-independent and resistant to treatment with antiestrogens. Transient transfection of ER-positive breast cancer cell lines T47D and MCF7 with G1/S cyclins could overcome the growth arrest induced by ICI 182780 treatment. The ability of various cyclin D1 mutants to overcome the ICI 182780 mediated growth arrest corresponded with their ability to stimulate cyclin A-and E2F-promoter based reporter activities in the presence of ICI 182780. Transfection of a mutant cyclin D1 (cyclin D1-KE) that was unable to bind CDK4 and was reported to transactivate ER in the presence of ICI 182780, could not stimulate proliferation in ICI 182780 treated cells. On the other hand, cyclin D1-LALA, which is unable to stimulate ERE transactivation, could overcome the ICI 182780 cell cycle arrest. Furthermore, transient transfection of T47D cells using cyclin D1 together with a catalytic inactive mutant of CDK4 (CDK4-DN) indicated that the observed effect is due to binding to CDK inhibitors. However, a moderate, sixfold overexpression of cyclin D1 in stably transfected MCF7 cells did not overcome the ICI 182780 mediated growth arrest. These results indicate that CDK-independent transactivation of the estrogen receptor by cyclin D1 is by itself, not sufficient to result in estradiol-independent growth of breast cancer cells, whereas a vast overexpression of G1/S cyclins is able to do so, most likely by capturing of CDK inhibitors.

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Section: Discussionmentioning

confidence: 68%

Involvement of G1/S cyclins in estrogen-independent proliferation of estrogen receptor-positive breast cancer cells

et al. 2002

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“…A way to overcome tamoxifen-induced cell cycle arrest could be by loss of pRb function [33]. As illustrated in Fig.…”

Section: Expression Of Cell Cycle Proteins In Mtr Variantsmentioning

confidence: 99%

Cyclin D1 expression is dependent on estrogen receptor function in tamoxifen-resistant breast cancer cells

Kilker

Hartl

Rutherford

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…Though the mechanism of tamoxifen-induced cell cycle arrest is still uncertain, it is thought to be mediated by ERα based on the observation that ER-negative cells are not as sensitive to tamoxifen as ER-positive cells [112]. Treatment of ER-positive, p53 wild-type cells with tamoxifen resulted in a dose-dependent increase of p53 and p21 proteins suggesting that a p53-dependent G1 cell cycle arrest pathway is activated [1, 113]. Addition of estrogen to tamoxifen-treated G1 arrested cells induced the cells to progress into S phase along with an increase in protein levels of cyclin D1 and the kinase activity of cyclin D1/CDK4 and cyclin D1/CDK2 [114-118].…”

Section: Er and P53 In Hormone-dependent Cancersmentioning

confidence: 99%

The p53-Estrogen Receptor Loop in Cancer

Berger

Qian

Chen

2013

CMM

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Tumor suppressor p53 maintains genome stability by regulating diverse cellular functions including cell cycle arrest, apoptosis, senescence and metabolic homeostasis. Mutations in the p53 gene occur in almost all human cancers with a frequency up to 80%. However, it is only 20% in breast cancers, 18% in endometrial cancers and 1.5% in cervical cancers. Estrogen receptor alpha (ERα) plays a pivotal role in hormonedependent cancer development and the status of ERα is used for designing treatment strategy and for prognosis. A closer look at the cross-talk between p53 and ERα has revealed that their activities are mutually regulated. This review will summarize the current body of knowledge on p53, ERα and ERβ in cancer. Clinical correlations between estrogen receptors and p53 status have also been reported. Thus, this review will discuss the relationship between p53 and ERs at both the molecular and clinical levels.

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Reversal of an antiestrogen-mediated cell cycle arrest of MCF-7 cells by viral tumor antigens requires the retinoblastoma protein-binding domain

Cited by 22 publications

References 48 publications

Involvement of G1/S cyclins in estrogen-independent proliferation of estrogen receptor-positive breast cancer cells

Involvement of G1/S cyclins in estrogen-independent proliferation of estrogen receptor-positive breast cancer cells

Cyclin D1 expression is dependent on estrogen receptor function in tamoxifen-resistant breast cancer cells

The p53-Estrogen Receptor Loop in Cancer

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