Journal Article

Mst1, RanBP2 and eIF4G are new markers for <i>in vivo</i> PI3K activation in murine and human prostate

Oliver Renner, Jesus Fominaya, Soledad Alonso, Carmen Blanco-Aparicio, Juan F.M. Leal and Amancio Carnero

in Carcinogenesis

Volume 28, issue 7, pages 1418-1425
Published in print July 2007 | ISSN: 0143-3334
Published online March 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm059
Mst1, RanBP2 and eIF4G are new markers for in vivo PI3K activation in murine and human prostate

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Phosphatidylinositol 3-kinases (PI3Ks) constitute important regulators of signaling pathways. The PIK3CA gene encoding the p110-alpha catalytic subunit represents one of the highly mutated oncogenes identified in human cancer. Here, we report new markers for in vivo PI3K activation in prostate. To that end, we used a transgenic mouse line, which expresses a constitutively active p110-alpha subunit in the epithelial cells of the prostate. The activity of the PI3K pathway in the prostate was proven by assessing the phosphorylation of the PI3K direct target AKT1 and of the mTOR target eukaryotic translation initiation factor 4G (eIF4G). To establish also transcriptional (‘late’) targets of the PI3K pathway, we tested two genes, Mst1 and RanBP2, which we recently described as transcriptional targets of the growth factor platelet-derived growth factor-beta. We show that the levels of both proteins are elevated in transgenic animals. Additionally, we describe that the phosphorylation of AKT and eIF4G, as well as the elevation of the Mst1 and RanBP2 protein levels, can be inhibited in vivo in transgenic animals by the PI3K inhibitor LY294002. Finally, we performed human tissue microarray experiments with the four markers. Since they define overlapping but not identical subsets of the tested tissue panel, a combination of all four markers might lead to a more accurate diagnosis of the status of the PI3K-signaling cascade in cancer patients.

Journal Article.  4972 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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