Estrogen-dependent cyclin E-cdk2 activation through p21 redistribution
- PMID: 9199341
- PMCID: PMC232259
- DOI: 10.1128/MCB.17.7.4059
Estrogen-dependent cyclin E-cdk2 activation through p21 redistribution
Abstract
In order to elucidate the mechanisms by which estrogens and antiestrogens modulate the growth of breast cancer cells, we have characterized the changes induced by estradiol that occur during the G1 phase of the cell cycle of MCF-7 human mammary carcinoma cells. Addition of estradiol relieves the cell cycle block created by tamoxifen treatment, leading to marked activation of cyclin E-cdk2 complexes and phosphorylation of the retinoblastoma protein within 6 h. Cyclin D1 levels increase significantly while the levels of cyclin E, cdk2, and the p21 and p27 cdk inhibitors are relatively constant. However, the p21 cdk inhibitor shifts from its association with cyclin E-cdk2 to cyclin D1-cdk4, providing an explanation for the observed activation of the cyclin E-cdk2 complexes. These results support the notion that cyclin D1 has an important role in steroid-dependent cell proliferation and that estrogen, by regulating the activities of G1 cyclin-dependent kinases, can control the proliferation of breast cancer cells.
Similar articles
-
Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2.J Biol Chem. 1997 Apr 18;272(16):10882-94. doi: 10.1074/jbc.272.16.10882. J Biol Chem. 1997. PMID: 9099745
-
Multifaceted regulation of cell cycle progression by estrogen: regulation of Cdk inhibitors and Cdc25A independent of cyclin D1-Cdk4 function.Mol Cell Biol. 2001 Feb;21(3):794-810. doi: 10.1128/MCB.21.3.794-810.2001. Mol Cell Biol. 2001. PMID: 11154267 Free PMC article.
-
Induction of G1 phase arrest in MCF human breast cancer cells by pentagalloylglucose through the down-regulation of CDK4 and CDK2 activities and up-regulation of the CDK inhibitors p27(Kip) and p21(Cip).Biochem Pharmacol. 2003 Jun 1;65(11):1777-85. doi: 10.1016/s0006-2952(03)00156-4. Biochem Pharmacol. 2003. PMID: 12781329
-
Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells.Endocr Relat Cancer. 2003 Jun;10(2):179-86. doi: 10.1677/erc.0.0100179. Endocr Relat Cancer. 2003. PMID: 12790780 Review.
-
Perspectives for cancer therapies with cdk2 inhibitors.Drug Resist Updat. 2001 Dec;4(6):347-67. doi: 10.1054/drup.2001.0224. Drug Resist Updat. 2001. PMID: 12030783 Review.
Cited by
-
Underdeveloped uterus and reduced estrogen responsiveness in mice with disruption of the estrogen-responsive finger protein gene, which is a direct target of estrogen receptor alpha.Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12027-32. doi: 10.1073/pnas.96.21.12027. Proc Natl Acad Sci U S A. 1999. PMID: 10518570 Free PMC article.
-
Early increase in cyclin-D1 expression and accelerated entry of mouse hepatocytes into S phase after administration of the mitogen 1, 4-Bis[2-(3,5-Dichloropyridyloxy)] benzene.Am J Pathol. 2000 Jan;156(1):91-7. doi: 10.1016/S0002-9440(10)64709-8. Am J Pathol. 2000. PMID: 10623657 Free PMC article.
-
Functional ablation of pRb activates Cdk2 and causes antiestrogen resistance in human breast cancer cells.PLoS One. 2007 Dec 5;2(12):e1256. doi: 10.1371/journal.pone.0001256. PLoS One. 2007. PMID: 18060053 Free PMC article.
-
c-Myc or cyclin D1 mimics estrogen effects on cyclin E-Cdk2 activation and cell cycle reentry.Mol Cell Biol. 1998 Aug;18(8):4499-508. doi: 10.1128/MCB.18.8.4499. Mol Cell Biol. 1998. PMID: 9671459 Free PMC article.
-
High miR-26a and low CDC2 levels associate with decreased EZH2 expression and with favorable outcome on tamoxifen in metastatic breast cancer.Breast Cancer Res Treat. 2012 Jun;133(3):937-47. doi: 10.1007/s10549-011-1877-4. Epub 2011 Nov 18. Breast Cancer Res Treat. 2012. PMID: 22094936 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials