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Moorehead, Roger A., Hojilla, Carlo V., De Belle, Ian, Wood, Geoffrey A., Fata, Jimmie E., Adamson, Eileen D., Watson, Katrina L., Edwards, Dylan R. 
ORCID: https://orcid.org/0000-0002-3292-2064 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
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: | 24 Sep 2024 10:12 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/718 |
| DOI: | 10.1074/jbc.M306894200 |
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