Prostate cancer is the second leading cause of death in men in the United States. It depends on the signaling by the androgen receptor (AR), which is activated by testosterone. AR signaling promotes normal prostate development as well as cancer. Current treatments for prostate cancer include prostatectomy and androgen deprivation therapy. Although androgen deprivation is effective in halting prostate cancer growth, a group of men are often diagnosed with castration resistant prostate cancer (CRPC), which is refractory to hormone deprivation. Therefore, new targets are needed to stop prostate cancer growth. In this study, we investigated whether Homeodomain‐interacting protein kinase 2 (HIPK2) affects AR signaling and prostate cancer cell growth. To do this, we utilized doxycycline‐induced shRNA‐mediated silencing of HIPK2 expression in 22Rv1 and LNCaP‐95, two cell lines that are refractory to androgen deprivation, and demonstrated substantial knockdown of both HIPK2 mRNA and protein. In addition, we observed significant changes in AR target gene expression. To determine the effects of HIPK2 knockdown on AR subcellular localization, we fractionated control and doxycycline‐treated 22Rv1 and LNCaP‐95 cells. We observed modest changes in chromatin‐bound AR upon HIPK2 depletion, suggesting that HIPK2 influences AR chromatin occupancy and in turn AR‐dependent transcription. We also tested HIPK2 catalytic inhibitors by examining their effects on 22Rv1 and LNCaP‐95 cellular proliferation, and phosphorylation a HIPK2 substrate, SIAH2. We found that HIPK2 inhibitors modestly affected the proliferation and substrate phosphorylation. Thus, HIPK2 can modulate AR activity, highlighting the role of HIPK2 as a new drug target for prostate cancer.Support or Funding InformationNew York University Langone Medical CenterThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Biomarkers have become a potential tool in the diagnosis of cancer patients, allowing a more accurate diagnosis and treatment. Prostate cancer is the second most common type of cancer in men worldwide. In prostate cancer, it is important to identify which patients would benefit from early treatment. Here we report the combination of phosphorylation of the retinoblastoma protein (Rb) on serine 249 (Rb S249) wit with p39 expression as biomarkers for predicting prostate cancer. We performed an immunohistochemical analysis of Rb S249 and p39 expression. Our results indicate that there is an inverse relationship between Rb S249 and prostate adenocarcinoma. Hence, Rb S249 could help in determining a more accurate prognosis for prostate cancer patients.Support or Funding InformationFunded by NIH‐NIGMS #2R25GM096955This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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