Abstract

Abstract One of the reasons for the most prostate cancer-related deaths is the growth of secondary tumors due to metastases and not the primary organ-confined carcinoma. Metastasis in cancer cells results in acquiring abilities of increased motility and invasiveness, to home in other parts of the body. The key regulator involved in the control of metastasis genes in prostate cancer is presently unknown. Special AT-rich sequence-binding protein 1 (SATB1) is a transcription factor and functions as genome organizer. SATB1 being a transcription factor tend to bind with AT rich base unpaired sequences of the target gene. SATB1 acquires a “3 D chickenwire” network by forming anchor loops around chromatin, recruits chromatin remodeling complexes on the anchorage sites, and regulates histone modifications by rendering DNA sequences accessible or inaccessible for transcription. Earlier studies suggested the role of SATB1 in breast cancer progression. We aimed to observe the role of SATB1 in prostate cancer progression. We used different grades of human prostate cancer specimens, non tumorigenic and aggressive prostate cancer cells. Immunohistochemical evaluation of SATB1 in prostate cancer specimens of various Gleason grades exhibited significantly increased expression with increase in Gleason grade. A progressive increase in nuclear SATB1 expression was observed as tumor grade increased along with its presence in the cytoplasm. Further, SATB1 protein levels were higher in human prostate cancer cell lines viz. HPV-CA-10, DU145, DUPro, PC-3, PC-3M compared to non-tumorigenic prostate epithelial cells PZ-HPV-7. Nuclear expression of SATB1 was higher in biologically aggressive subclones of prostate cancer cells. Introduction of SATB1 through transient infections into non-tumorigenic PZ-HPV-7 cells increased its invasiveness and migration capabilities, whereas these properties were inhibited by silencing SATB1 through shRNA techniques. Furthermore, knock down of SATB1 caused increased E-cadherin expression and simultaneous reduction in matrix metalloproteinase-9 expression, providing further evidence that SATB1 significantly influences the metastasis process. Taken together, our results suggest that SATB1 is a master regulator of the metastasis process in prostate cancer and, therefore, could be considered as an independent prognostic factor and a potential therapeutic target for prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2364.

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