Loss of the SSeCKS/Gravin/AKAP12 gene results in prostatic hyperplasia.
Loss of the SSeCKS/Gravin/AKAP12 gene results in prostatic hyperplasia.
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DOI：
10.1158/0008-5472.can-07-5619
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发表时间：
2008-07-01
期刊：
影响因子：
11.2
通讯作者：
Gelman IH
中科院分区：
文献类型：
--
作者：
Akakura S;Huang C;Nelson PJ;Foster B;Gelman IH
SSeCKS/Gravin/AKAP12 （SSeCKS）是一种激酶支架蛋白，通过抑制src介导的致癌信号和血管内皮生长因子的表达来编码转移抑制活性。SSeCKS在Src和ras转化成纤维细胞、人类癌细胞系和几种人类癌症（包括前列腺癌）中表达下调。正常的人和小鼠前列腺在分泌性上皮细胞中表达丰富的SSeCKS，在周围的间质中表达较少。在这里，我们发现SSeCKS的缺失导致前列腺前叶和腹叶的增生，以及整个前列腺细胞凋亡水平的增加。发育不良灶的观察频率较低，但与e -钙粘蛋白染色的丧失和高分子量细胞角蛋白阳性基底上皮细胞的丧失有关。与野生型对照相比，SSeCKS缺失的前列腺组织中AKTpoS473的相对表达水平显著升高，这表明SSeCKS减弱了磷脂酰肌醇-3- oh激酶信号传导。数据表明，ssecks缺失小鼠对前列腺癌转化的易感性增加。
SSeCKS/Gravin/AKAP12 (SSeCKS) is a kinase scaffolding protein that encodes metastasis-suppressor activitythrough 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 AKTpoS473 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.