✦ LIBER ✦

Deregulation of the cell cycle by breast tumor kinase (Brk)

✍ Scribed by Edward Chan; Anjaruwee S. Nimnual

Book ID: 102864060
Publisher: John Wiley and Sons
Year: 2010
Tongue: French
Weight: 560 KB
Volume: 127
Category: Article
ISSN: 0020-7136
DOI: 10.1002/ijc.25263

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✦ Synopsis

Abstract

Brk is a cytoplasmic nonreceptor tyrosine kinase that is overexpressed in breast tumors but undetectable in normal or benign mammary tissues. Brk promotes proliferation of human mammary epithelial cells and tumor growth in a mouse model, but the role of Brk in cell cycle regulation is not known. In this study, we describe the mechanism of Brk‐induced deregulation of the cell cycle. We provide evidence that Brk antagonizes the transcriptional activity of the transcription factor FoxO family of proteins by inhibiting its nuclear localization. As a result, the cell cycle inhibitor p27, a FoxO target gene, is down‐regulated. This event is accompanied by G1/S cell cycle progression of quiescent cells. As p27 is a key regulator of the G1/S cell cycle checkpoint, these data suggest that perturbation of p27 expression induced by Brk causes S phase entrance. Deregulation of the cell cycle is a key event in neoplasia, and thus, the mechanism presented here likely contributes to breast cancer development.

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