Androgen receptor is a primary
transcription factor involved in the proliferation of
prostate cancer cells. Thus,
hormone therapy using
antiandrogens, such as
bicalutamide, is a first-line treatment for the disease. Although
hormone therapy initially reduces the
tumor burden, many patients eventually relapse, developing
tumors with acquired endocrine resistance. Elucidation of the molecular mechanisms underlying endocrine resistance is therefore a fundamental issue for the understanding and development of alternative
therapeutics for advanced
prostate cancer. In the present study, we performed
short hairpin RNA (
shRNA)-mediated functional screening to identify genes involved in
bicalutamide-mediated effects on LNCaP
prostate cancer cells. Among such candidate genes selected by screening using volcano plot analysis,
ribosomal protein L31 (
RPL31) was found to be essential for cell proliferation and cell-cycle progression in
bicalutamide-resistant LNCaP (BicR) cells, based on
small interfering RNA (
siRNA)-mediated knockdown experiments. Of note,
RPL31 mRNA is more abundantly expressed in BicR cells than in parental LNCaP cells, and clinical data from ONCOMINE and The
Cancer Genome Altas showed that
RPL31 is overexpressed in prostate
carcinomas compared with benign prostate tissues. Intriguingly,
protein levels of the
tumor suppressor p53 and its targets, p21 and MDM2, were increased in LNCaP and BicR cells treated with
RPL31 siRNA. We observed decreased degradation of p53
protein after
RPL31 knockdown. Moreover, the suppression of growth and cell cycle upon
RPL31 knockdown was partially recovered with p53
siRNA treatment. These results suggest that
RPL31 is involved in
bicalutamide-resistant growth of
prostate cancer cells. The
shRNA-mediated functional screen in this study provides new insight into the molecular mechanisms and therapeutic targets of advanced
prostate cancer.