Abstract A24: Epigenetic silencing of ID4 (inhibitor of DNA binding 4) is associated with prostate cancer

Abstract

Abstract Introduction: Inhibitor of DNA binding/differentiation protein 4 (Id4) is dominant negative regulator of basic helix loop helix (bHLH) family of transcription factors. Id4 shares the homology of HLH domain with other Ids and lack the basic DNA binding region. Previous studies from our lab had shown that unlike Id1, Id2 and Id3, Id4 acts as a tumor suppressor in prostate cancer by attenuating cell proliferation and promote apoptosis. Consistent with these observations Id4 is epigenetically silenced in Du145 prostate cancer cell line. In this study we investigated whether Id4 is also epigenetically silenced in prostate cancer. We also examined association between Id4 promoter hypermethylation and its expression in prostate cancer cell lines. Experimental procedures: Id4 protein expression was analyzed on human prostate adenocarcinoma samples by Immunhistochemistry. Id4 promoter methylation pattern on prostate cancer cell lines (C33, C81, DU145, LNCaP, DU145+ID4, and PC3) was examined. In addition, we performed Laser capture microdisection (LCMD) on the human prostate tissues and methylation specific PCR to correlate our cell line studies with clinical studies. Results: IHC demonstrated decreased Id4 protein expression in human prostate tissue samples whereas higher nuclear Id4 expression was found in normal prostate tissues.Id4 methylation specific PCR (MSP) on prostate cancer cell lines, showed Id4 methylation in DU145 cell and but not in LNCaP and C33 cells. In C81 and PC3 cells it showed partial methylation. C81 are derivatives of LNCaP cell lines and are Androgen independent and are more metastatic. Increased Id4 methylation in C81 as compared to LNCaP suggests its epigenetic silencing as cells acquire androgen independence. Tumors with Id4 promoter hypermethylation showed distinct loss of Id4 expression. Conclusions: Id4 appears as a potential tumor suppressor gene that is epigenetically silenced during cancer development.Id4 promoter hypermethylation had been reported in breast, colorectal cancer and chronic lymphocytic leukemia Thus, loss of Id4 expression due to promoter hypermethylation. Id4 methylation status could serve as a prognostic biomarker in human prostate cancer. Acknowledgement: The research was supported by NIH/NCI-RO1CA128914 and in part by NIH/NCRR/RCMI G12RR03062. Citation Format: Pankaj Sharma, Swathi Chinaranagari, Divya Patel, Jaideep Chaudhary. Epigenetic silencing of ID4 (inhibitor of DNA binding 4) is associated with prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A24.