Loss of the SSeCKS/Gravin/AKAP12 gene results in prostatic hyperplasia.
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.
Akakura
Shin
S
Department of Cancer Genetics, Therapeutics Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Huang
Changhui
C
Nelson
Peter J
PJ
Foster
Barbara
B
Gelman
Irwin H
IH
D054758:A Kinase Anchor Proteins / Q000235:genetics*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011470:Prostatic Hyperplasia / Q000235:genetics*; D019076:Transgenes
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D018797:Cell Cycle Proteins