Critical role of cyclin B1/Cdc2 up-regulation in the induction of mitotic prometaphase arrest in human breast cancer cells treated with 2-methoxyestradiol.

Biochimica Et Biophysica Acta
Hye Joung Choi, Bao Ting Zhu

Abstract

Earlier studies showed that 2-methoxyestradiol (2ME(2)), an endogenous nonpolar metabolite of estradiol-17β, is a strong inducer of G(2)/M cell cycle arrest (based on analysis of cellular DNA content) in human cancer cell lines. The present study sought to investigate the molecular mechanism underlying 2ME(2)-induced cell cycle arrest. We found that 2ME(2) can selectively induce mitotic prometaphase arrest, but not G(2) phase arrest, in cultured MDA-MB-435s and MCF-7 human breast cancer cells. During the induction of prometaphase arrest, there is a time-dependent initial up-regulation of cyclin B1 and Cdc2 proteins, occurring around 12-24h. The strong initial up-regulation of cyclin B1 and Cdc2 matches in timing the 2ME(2)-induced prometaphase arrest. The 2ME(2)-induced prometaphase arrest is abrogated by selective knockdown of cyclin B1 and Cdc2, or by pre-treatment of cells with roscovitine, an inhibitor of cyclin-dependent kinases, or by co-treatment of cells with cycloheximide, a protein synthesis inhibitor that was found to suppress the early up-regulation of cyclin B1 and Cdc2. In addition, we provided evidence showing that MAD2 and JNK1 are important upstream mediators of 2ME(2)-induced up-regulation of cyclin B1 and Cdc...Continue Reading

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Citations

Apr 26, 2014·Hormones & Cancer·Mauricio P PintoGareth I Owen
Nov 13, 2012·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Marisol QuezadaMiguel L Allende
Aug 1, 2015·Journal of Cellular and Molecular Medicine·Renáta MinoricsIstván Zupkó
Aug 8, 2015·Journal of Clinical Pathology·Jin Hyung HeoHee Jung An
Mar 24, 2018·Cellular & Molecular Biology Letters·Laura Susan BoydAnna Margaretha Joubert
Dec 12, 2012·Molecular Medicine Reports·Xiang-Yong QueXin-Zhi Li
Nov 10, 2017·Cancer Cell International·Lisa RepsoldAnnie Margaretha Joubert
Dec 31, 2020·International Journal of Molecular Sciences·Yao-Feng LiChia-Kuang Tsai

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