Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 319, Issue 1-2, Pages 129-142Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2010.01.019
Keywords
BRCA1; Estrogen; Breast cancer; AKT; IGF1; Proteasome; Phosphorylation
Categories
Funding
- Department of Defense [W81XWH-06-1-0335, DAMD17-02-1-0351, W81XWH-06-1-0423]
- Public Health Service [DK063674]
Ask authors/readers for more resources
The observation that inherited mutations within BRCA1 result in breast and ovarian cancers suggests a functional relationship may exist between hormone signaling and BRCA1 function We demonstrate that AKT activation promotes the expression of BRCA1 in response to estrogen and IGF-1 receptor signaling, and the rapid increase in BRCA1 protein levels appears to occur independently of new protein synthesis Further, we identify a novel AKT phosphorylation site in BRCA1 at S694 which is responsive to activation of these signaling pathways These data suggest Ala phosphorylation of BRCA1 increases total protein expression by preventing proteasomal degradation AKT activation also appears to support nuclear localization of BRCA1. and co-expression of activated AKT with BRCA1 decreases radiation sensitivity, suggesting this interaction has functional consequences for BRCA1's role in DNA repair. Targets within this pathway could provide strategies for modulation of BRCA1 protein, which may prove therapeutically beneficial for breast and ovarian cancer treatment. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available