J Breast Cancer.  2010 Dec;13(4):382-391. 10.4048/jbc.2010.13.4.382.

Molecular Mechanism of the G2/M Arrest in Breast Cancer Cell Lines (T47D and MDA-MB231) Induced by Genistein

Affiliations
  • 1Department of Pathology, Kyungpook National University School of Medicine, Daegu, Korea. yksohn@knu.ac.kr

Abstract

PURPOSE
To analyze the effect of the growth control on human breast cancer cells with genistein treatment and to investigate the mechanism of genistein-induced G2/M arrest in T47D and MDA-MB231 breast carcinoma cells by Cdc25C expression.
METHODS
We analysed the proliferartion of the two cell lines by using MTT proliferation assay, flow cytometric analysis, real-time quantitative RT-PCR and western blotting and investigated the effect of genistein on cell survival, cellular toxicity, cell cycle progression-related genes and their mRNA and protein alterations.
RESULTS
The DNA flow cytometric analysis of both cell lines treated with genistein showed a dose-dependent growth inhibition and accumulation in the G2/M phase of cell cycle. The expression of p21 mRNA and protein increased in both cell lines following genistein treatment but p27 expression was unchanged. Furthermore, decreased Cdc25C expression with decreased polo-like kinase (PLK) 1 expression and increased PLK3 expression were observed after genistein treatment. The decreased level of Cdc25C in the nucleus was associated with decreased phosphorylation of Cdc25C by PLK1. The expression of PLK3 was increased with a dose-dependent and a time-dependent manner and was associated with decreased Cdc25C expression. Check point kinase (CHK) 1 and CHK2 revealed different expression patterns each other. The CHK1 expression was independent of the presence of genestein. CHK2 expression increased in MDA-MB231 cells associated with decreased Cdc25C expression but not in T47D.
CONCLUSION
These results suggest that genistein induces a G2/M arrest in human breast cancer cells, the mechanism of which is due, in part, to decreased in Cdc25C phosphatase by a regulatory effect of PLK1, PLK3, and CHK2 as well as increased expression of the cyclin dependent kinase inhibitor p21(WAF1/CIP1).

Keyword

Breast neoplasms; Cell cycle; Genistein

MeSH Terms

Blotting, Western
Breast
Breast Neoplasms
cdc25 Phosphatases
Cell Cycle
Cell Line
Cell Survival
Cyclins
DNA
Genistein
Humans
Phosphorylation
Phosphotransferases
RNA, Messenger
Cyclins
DNA
Genistein
Phosphotransferases
RNA, Messenger
cdc25 Phosphatases
Full Text Links
  • JBC
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2022 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr