Antiestrogen inhibition of cell cycle progression in breast cancer cells in associated with inhibition of cyclin-dependent kinase activity and decreased retinoblastoma protein phosphorylation

Molecular Endocrinology
C K WattsR L Sutherland

Abstract

To define the mechanisms by which antiestrogens inhibit breast cancer cell proliferation, the effects of the antiestrogen ICI 182780 on G1 cyclins and their cyclin-dependent kinase (CDK) partners were investigated in MCF-7 cells. Inhibition of entry into S phase became evident 9 h after treatment, with the proportion of cells in S phase reaching a minimum by 24 h. ICI 182780 increased the proportion of the hypophosphorylated, growth inhibitory form of the retinoblastoma protein (pRB). This change began at 4-6 h, preceding effects on S phase. This suggests that there are early effects on the activities of CDKs that target pRB that are not merely a consequence of changes in cell cycle progression. The kinase activity of Cdk2 decreased to low levels at 18-24 h when changes in S phase and pRB phosphorylation were well advanced. An earlier effect was seen on kinase activity associated with immunoprecipitated cyclin D1, which was reduced approximately 40% by 12 h, with further decreases at 18-24 h. Cdk2 and Cdk4 protein levels remained constant over 24 h. Cyclin D1 messenger RNA and protein were down-regulated by ICI 182780 from 2 h, with levels halved at 8 h. ICI 182780 also increased the expression of the CDK inhibitors p27KIP1 and...Continue Reading

Citations

Jan 15, 2009·Nature Reviews. Cancer·Erik S Knudsen, Karen E Knudsen
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·S CariouJ M Slingerland
Apr 8, 1999·Molecular Pathology : MP·P L FernándezA Cardesa
Dec 13, 2006·The Journal of Clinical Investigation·Emily E BoscoErik S Knudsen
Jan 14, 2010·Breast Cancer Research : BCR·Robert L Sutherland, Elizabeth A Musgrove
Mar 4, 2011·Endocrine-related Cancer·Chellappagounder ThangavelErik S Knudsen
Oct 20, 2006·Breast Cancer Research and Treatment·Keren HirschYoav Sharoni
Mar 28, 2006·European Journal of Nutrition·Amit NahumYoav Sharoni
Jan 1, 1996·Cancer Treatment and Research·K J SweeneyR L Sutherland
Sep 5, 2003·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Junichi KohMasaki Kitajima
Nov 16, 2011·Bulletin of Mathematical Biology·Kate SimmsAdrian Koerber
Feb 27, 2015·Current Oncology Reports·Erica L Mayer
Sep 17, 2014·Breast Cancer Research : BCR·Agnieszka K Witkiewicz, Erik S Knudsen
Jan 20, 2000·Journal of the National Cancer Institute·A BrinkmanL C Dorssers
Oct 19, 2006·American Journal of Physiology. Endocrinology and Metabolism·Ruijin ShaoHåkan Billig
Aug 21, 2021·Journal of Medicinal Chemistry·Leah L LowderSridhar Varadarajan

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