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Publication : Loss of the SSeCKS/Gravin/AKAP12 gene results in prostatic hyperplasia.

First Author  Akakura S Year  2008
Journal  Cancer Res Volume  68
Issue  13 Pages  5096-103
PubMed ID  18593908 Mgi Jnum  J:138882
Mgi Id  MGI:3806754 Doi  10.1158/0008-5472.CAN-07-5619
Citation  Akakura S, et al. (2008) Loss of the SSeCKS/Gravin/AKAP12 gene results in prostatic hyperplasia. Cancer Res 68(13):5096-103
abstractText  SSeCKS/Gravin/AKAP12 (SSeCKS) is a kinase scaffolding protein that encodes metastasis-suppressor activity through the suppression of Src-mediated oncogenic signaling and vascular endothelial growth factor expression. SSeCKS expression is down-regulated in Src- and Ras-transformed fibroblasts, in human cancer cell lines and in several types of human cancer, including prostate. Normal human and mouse prostates express abundant SSeCKS in secretory epithelial cells and, to a lesser extent, in the surrounding mesenchyme. Here, we show that the loss of SSeCKS results in prostatic hyperplasia in the anterior and ventral lobes as well as increased levels of apoptosis throughout the prostate. Dysplastic foci were observed less frequently but were associated with the loss of E-cadherin staining and the loss of high molecular weight cytokeratin-positive basal epithelial cells. SSeCKS-null prostate tissues expressed significantly higher relative levels of AKT(poS473) compared with wild-type controls, suggesting that SSeCKS attenuates phosphatidylinositol-3-OH kinase signaling. The data suggest that SSeCKS-null mice have increased susceptibility for oncogenic transformation in the prostate.
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