Abstract
Abstract Prostate cancer is the most common cancer for men in the US. It is well known that the androgen receptor (AR), a master transcription factor in prostate, plays a critical role in all stages of prostate cancer. There has been a dedicated interest in identification of downstream AR target genes responsible for prostate cancer growth and progression. Using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq), we identified WNT7B as a direct AR target gene in both androgen-dependent LNCaP and androgen-independent C4-2B cells. Knockdown of WNT7B by RNA interference inhibits the growth of LNCaP and C42B cells, accompanied by a corresponding increase in apoptosis as determined by Caspase-3 and -7 activities. Overexpression of WNT7B promotes the growth of C4-2B cells in the absence of androgen. One of the major challenges in prostate cancer research is the propensity for bone metastasis, which displays characteristic osteoblastic lesions. Since WNT7B plays an important role in bone formation, we asked whether prostate cancer-produced WNT7B induces osteoblast differentiation using an in vitro model of the murine osteoblast precursor ST2 cell line. We found that in a co-culture system, overexpression of WNT7B in LNCaP and C42B cells induces osteoblastic differentiation of ST2 cells, as indicated by increased alkaline phosphatase production, bone sialoprotein (an early marker for osteoblast differentiation) expression, and mineralization. On the other hand, knockdown of WNT7B in prostate cancer cells inhibits the differentiation of ST2 cells. These results indicate that WNT7B can stimulate the growth of prostate cancer cells as an autocrine agent and induce osteoblastic differentiation in bone metastases as a paracrine agent. WNT7B may be a potential therapeutic target for prostate cancer bone metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-300. doi:1538-7445.AM2012-LB-300
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