Targeted Elimination of PCDH-PC Expressing Prostate Cancer Cells for Control of Hormone-Resistant Prostate Cancer

摘要

Protocadherin-PC (PCDH-PC or PCDH11Y) is a human-, male-specific gene product that is upregulated in prostate cancer cells by androgen deprivation therapy. Silencing of this gene product with PCDH-PC-specific siRNA drastically induced the death of prostate cancer cells cultured in the absence of androgens and we have proposed that PCDH-PC expression knockout by shRNAs or antisense oligonucleotides (ASOs) might be useful in preventing the development of castration-recurrent prostate cancer in prostate cancer patients. To this end, we have created functional shRNA vectors and ASOs capable of suppressing PCDH-PC expression and we have also created a monoclonal antibody that allows us to detect PCDH-PC protein in cell extracts or tissues. The antibody preferentially recognizes prostate cancer cells in human prostate specimens. Knockdown of PCDH-PC expression by the shRNA vectors is more efficient than with siRNA and is apparently sufficient to kill prostate cancer cells even under conditions where androgen is available and this further supports the idea that PCDH-PC contributes to the biological properties and survival of prostate cancer cells.