NDLI: PTEN and p53 cross-regulation induced by soy isoflavone genistein promotes mammary epithelial cell cycle arrest and lobuloalveolar differentiation

Content Provider	PubMed Central
Author	Rahal, Omar M. Simmen, Rosalia C. M.
Copyright Year	2010
Abstract	The tumor suppressors phosphatase and tensin homologue deleted on chromosome ten (PTEN) and p53 are closely related to the pathogenesis of breast cancer, yet pathway-specific mechanisms underlying their participation in mediating the protective actions of dietary bioactive components on breast cancer risk are poorly understood. We recently showed that dietary exposure to the soy isoflavone genistein (GEN) induced PTEN expression in mammary epithelial cells in vivo and in vitro, consistent with the breast cancer preventive effects of soy food consumption. Here, we evaluated PTEN and p53 functional interactions in the nuclear compartment of mammary epithelial cells as a mechanism for mammary tumor protection by GEN. Using the non-tumorigenic human mammary epithelial cells MCF10-A, we demonstrate that GEN increased PTEN expression and nuclear localization. We show that increased nuclear PTEN levels initiated an autoregulatory loop involving PTEN-dependent increases in p53 nuclear localization, PTEN–p53 physical association, PTEN–p53 co-recruitment to the PTEN promoter region and p53 transactivation of PTEN promoter activity. The PTEN–p53 cross talk induced by GEN resulted in increased cell cycle arrest; decreased pro-proliferative cyclin D1 and pleiotrophin gene expression and the early formation of mammary acini, indicative of GEN promotion of lobuloalveolar differentiation. Our findings provide support to GEN-induced PTEN as both a target and regulator of p53 action and offer a mechanistic basis for PTEN pathway activation to underlie the antitumor properties of dietary factors, with important implications for reducing breast cancer risk.
Related Links	http://dx.doi.org/10.1093/carcin/bgq123
Ending Page	1500
Page Count	10
Starting Page	1491
File Format	PDF
ISSN	01433334
e-ISSN	14602180
Journal	Carcinogenesis
Issue Number	8
Volume Number	31
Language	English
Publisher	Oxford University Press
Publisher Date	2010-08-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Cancer Research Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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