IGF-II regulates PTEN expression in the mammary gland

Moorehead, Roger A., Hojilla, Carlo V., De Belle, Ian, Wood, Geoffrey A., Fata, Jimmie E., Adamson, Eileen D., Watson, Katrina L., Edwards, Dylan R. and Khokha, Rama (2003) IGF-II regulates PTEN expression in the mammary gland. Journal of Biological Chemistry, 278 (50). pp. 50422-50427. ISSN 1083-351X

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Abstract

The tumor suppressor PTEN is altered in many cancers, including breast cancer, but only a handful of factors are known to control its expression. PTEN plays a vital role in cell survival and proliferation by regulating Akt phosphorylation, a key component of the phosphatidylinositol 3 kinase (PI3K) pathway. Here we show that insulin-like growth factor-II (IGF-II), which signals through PI3K, regulates PTEN expression in the mammary gland. IGF-II injection into mouse mammary gland significantly increased PTEN expression. Transgenic IGF-II expression also increased mammary PTEN protein, leading to reductions in Akt phosphorylation, epithelial proliferation, and mammary morphogenesis. IGF-II induced PTEN promoter activity and protein levels and this involved the immediate early gene egr-1. Thus, we have identified a novel negative feedback loop within the PI3K pathway where IGF-II induces PTEN expression to modulate its physiologic effects.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Cells and Tissues Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User:	EPrints Services
Date Deposited:	01 Oct 2010 13:37
Last Modified:	28 Mar 2025 04:36
URI:	https://ueaeprints.uea.ac.uk/id/eprint/718
DOI:	10.1074/jbc.M306894200

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