Abstract 4081: Id4 (inhibitor of dna binding 4) crosstalk with pten-akt pathway

Abstract

Abstract Introduction: Inhibitor of DNA binding/differentiation protein 4 (Id4), acts as a 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 promoting apoptosis. In this study we investigated whether Id4 acts as a tumor suppressor by regulating the AKT pathway. Experimental procedures: Id4 protein expression was analyzed on human prostate adenocarcinoma samples by Immunohistochemistry. We also performed Immunohistochemistry to determine AKT, pAKT, PTEN protein expression in Id4 knockout mouse prostates. In addition we determined the expression levels of the above mentioned proteins in prostate cancer cell lines with or without Id4 (LNCaP, LNCaP-Id4, DU145, DU145+Id4, PC3). Results: IHC demonstrated decreased Id4 protein expression in human prostate tissue samples whereas higher nuclear Id4 expression was found in normal human and mouse prostate tissues. IHC on Id4 knockout (Id4-/-) mouse prostates demonstrated an increase in pAKT expression, whereas AKT expression did not change significantly when compared to normal mouse prostate. PTEN expression levels decreased ignificantly in Id4 knockout mouse prostates. Similar pattern was observed in prostate cancer cell lines: DU145 cells lacking Id4 had low PTEN as compared to Id4 over-expressing DU145 cells. Id4 expression was also associated with PI3 kinase activity in LNCaP and PC3 cells. These results suggest Id4 regulates AKT-PI3K pathway by attenuating PTEN. Conclusions: Id4 appears as a potential tumor suppressor gene that exerts its tumor suppressor activity by promoting PTEN expression. PTEN in turn regulates AKT phosphorylation that stabilizes p53, AR and NKX3.1 expression in the normal prostate. Acknowledgement: The research was supported by NIH/NCI-RO1CA128914 and in part by NIH/NCRR/RCMI G12RR03062 Citation Format: Shravan Kumar Komaragiri. Id4 (inhibitor of dna binding 4) crosstalk with pten-akt pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4081. doi:10.1158/1538-7445.AM2014-4081