Prostate cancer: The Id1 story

Abstract

Id (inhibitor of differentiation or DNA binding) gene encodes a helix-loop helix protein which dimerizes and blocks the basic HLH protein from binding DNA. It expresses mainly in actively dividing cells and was first reported to be involved in hormone-induced prostate cancer in the Noble rat model. It was subsequently confirmed also in human prostate cancer. Through functional studies under in vitro system, they have further demonstrated the role of Id1 in prostate cancer progression. They have shown that Id1 transfection stimulated prostate cancer cell proliferation through downregulation of p16/Rb, while inducing activation of MAPK and NFκB pathways. Activation of the latter pathways by ectopic transfection of Id1 to LNCaP cells, an androgen dependent line, also resulted in reduced sensitivity of prostate cancer cells to androgen on the one hand and upregulating the expression of EGFR and PSA on the other hand, which are both hallmarks of androgen independent prostate cancer. This review shows the crucial role played by Id1 in the conversion of prostate cancer from androgen dependent to androgen independent stage.