PT - JOURNAL ARTICLE AU - JASON P. CAREY AU - ASHLEY EVANS KNOWELL AU - SWATHI CHINARANAGARI AU - JAIDEEP CHAUDHARY TI - Id4 Promotes Senescence and Sensitivity to Doxorubicin-induced Apoptosis in DU145 Prostate Cancer Cells DP - 2013 Oct 01 TA - Anticancer Research PG - 4271--4278 VI - 33 IP - 10 4099 - http://ar.iiarjournals.org/content/33/10/4271.short 4100 - http://ar.iiarjournals.org/content/33/10/4271.full SO - Anticancer Res2013 Oct 01; 33 AB - Inhibitor of differentiation proteins (Id1, 2, 3 and 4) are dominant negative regulators of basic helix loop helix transcription factors and play dominant roles in cancer cells, spanning several molecular pathways including senescence, invasion, metastasis, proliferation and apoptosis. In contrast to high Id1, Id2 and Id3 expression, the expression of Id4 is epigenetically silenced in prostate cancer. In the present study we demonstrated a novel role of Id4, that of promotion of cellular senescence in prostate cancer cells. Materials and Methods: Id4 was ectopically expressed in DU145 cells (DU145+Id4). The cells treated with Doxorubicin (0-500 nm) or vehicle control were analyzed for apoptosis, senescence (SA-beta Galactosidase), and expression of CDKN1A (p21), CDKN1B(p27), CDKN2A (p16), E2F1, vimentin and E-cadherin by immuno-histochemistry and/or Western blot. Results: In the present study we demonstrated that Id4 promotes cellular senescence in prostate cancer cell line DU145. Ectopic overexpression of Id4 in androgen receptor-negative DU145 prostate cancer cells resulted in increased expression of p16, p21, p27, E-cadherin and vimentin but down-regulated E2F1 expression. Id4 also potentiated the effect of doxorubicin induced senescence and apoptosis. Conclusion: The absence of functional p16, pRB and p53 in DU145 suggests that Id4 could alter additional molecular pathways such as those involving E2F1 to promote senescence and increased sensitivity to doxorubicin-induced apoptosis. The results of the present study support the role of Id4 as a tumor suppressor in prostate cancer.