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PIKE-A is required for prolactin-mediated STAT5a activation in mammary gland development


PI 3-kinase enhancer A (PIKE-A) is critical for the activation of Akt signalling, and has an essential function in promoting cancer cell survival. However, its physiological functions are poorly understood. Here, we show that PIKE-A directly associates with both signal transducer and activator of transcription 5a (STAT5a) and prolactin (PRL) receptor, which is essential for PRL-provoked STAT5a activation and the subsequent gene transcription. Depletion of PIKE-A in HC11 epithelial cells diminished PRL-induced STAT5 activation and cyclin D1 expression, resulting in profoundly impaired cell proliferation in vitro. To confirm the function of PIKE-A in PRL signalling in vivo, we generated PIKE knockout (PIKE?/?) mice. PIKE?/? mice displayed a severe lactation defect that was characterized by enhanced apoptosis and impaired proliferation of mammary epithelial cells. At parturition, STAT5 activation and cyclin D1 expression were substantially reduced in the mammary epithelium of PIKE?/? mice. The defective mammary gland development in PIKE?/? mice was rescued by overexpression of a mammary-specific cyclin D1 transgene. These data establish a critical function for PIKE-A in mediating PRL functions.

Type Journal
ISBN 1460-2075 (Electronic) 0261-4189 (Linking)
Authors Chan, C., Liu, X., Ensslin, M.A., Dillehay, D.L., Ormandy, C.J., Sohn, P., Serra, R.; Ye, K.:
Publisher Name EMBO JOURNAL
Published Date 2010-03-05
Published Volume 29
Published Issue 5
Published Pages 956-968
Status Published in-print
DOI 10.1038/emboj.2009.406
URL link to publisher's version
OpenAccess link to author's accepted manuscript version