Prostate Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Prostate Cancer, including details on symptoms, genetics, screening, treatment, information.

Regulation of mammalian target of rapamycin activity in PTEN-inactive prostate cancer cells by I kappa B kinase alpha.

Dan HC, Adli M, Baldwin AS

Lineberger Comprehensive Cancer Center, Department of Biology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.

The mammalian target of rapamycin (mTOR) is a mediator of cell growth, survival, and energy metabolism at least partly through its ability to regulate mRNA translation. mTOR is activated downstream of growth factors, insulin, and Akt-dependent signaling associated with oncoprotein expression or loss of the tumor-suppressor PTEN. In this regard, mTOR activity is associated with cancer cell growth and survival. Here, we have explored an involvement of the I kappa B kinase (IKK) pathway, associated with nuclear factor-kappaB activation, in controlling mTOR activity. The experiments show that IKK alpha controls mTOR kinase activity in Akt-active, PTEN-null prostate cancer cells, with less involvement by IKK beta. In these cells, IKK alpha associates with mTOR, as part of the TORC1 complex, in an Akt-dependent manner. Additionally, IKKalpha is required for efficient induction of mTOR activity downstream of constitutively active Akt expression. The results indicate a novel role for IKK alpha in controlling mTOR function in cancer cells with constitutive Akt activity.

Published 9 July 2007 in Cancer Res, 67(13): 6263-9.
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