Abstract LB-104: Prostate-specific inactivation of Atbf1 causes mouse prostatic intraepithelial neoplasia

Abstract

Abstract Cancer initiation and progression is triggered by loss of function of tumor suppressor genes. Previously, we have identified the AT-motif Binding Factor 1 (ATBF1) as a candidate tumor suppressor gene at 16q22 in the prostate. It undergoes frequent somatic mutations, reduced expression, or mislocalization in human cancers. However, its tumor suppressor role has not been examined in vivo. In the current study, we generated a conditional Atbf1 knockout mouse line using the Cre-loxP system. Tissue-specific inactivation of Atbf1 in prostatic epithelial cells caused hyperplasia in the dorsal lobes at as early as 4 months of age, which further progressed to mouse prostatic intraepithelial neoplasia (mPIN) in all four lobes. These precancerous lesions harbored molecular aspects similar to human PIN and prostate cancer, including increased cell proliferation, attenuated the basal cell layer, loss of the cell junction protein E-cadherin, and loss of an intact smooth muscle layer. Meanwhile, we observed elevated levels of Muc1 and p-Erk 1/2 in mPIN lesions. In addition, we identified and validated a number of genes that were disregulated in the Atbf1 knockout mice, and many of those genes encode secretory proteins. Supportively, an altered secretory protein profile was observed in the dorsal lobes. Taken together, our data demonstrated that loss of Atbf1 caused precancerous lesions in the prostate, thus providing in vivo evidence to a tumor suppressor role of the ATBF1 gene. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-104. doi:1538-7445.AM2012-LB-104