Prostate cancer is the second leading cause of
cancer-associated deaths among men in the western countries. Here, we report that human
RecQL4 helicase, which is implicated in the pathogenesis of a subset of
cancer-prone
Rothmund-Thomson syndrome, is highly elevated in metastatic
prostate cancer cell lines. Increased RecQL4 expression was also detected in human prostate
tumor tissues as a function of
tumor grade with the highest expression level in metastatic
tumor samples, suggesting that RecQL4 may be a potential prognostic factor for advanced stage of
prostate cancer. Transient and stable suppression of RecQL4 by
small interfering RNA and
short hairpin RNA vectors drastically reduced the growth and survival of metastatic
prostate cancer cells, indicating that RecQL4 is a prosurvival factor for
prostate cancer cells. RecQL4 suppression led to increased
poly(ADP-ribose) polymerase (PARP) synthesis and RecQL4-suppressed
prostate cancer cells underwent an extensive apoptotic death in a PARP-1-dependent manner. Most notably, RecQL4 knockdown in metastatic
prostate cancer cells drastically reduced their cell invasiveness in vitro and tumorigenicity in vivo, showing that RecQL4 is essential for
prostate cancer promotion. Observation of a direct interaction of
retinoblastoma (Rb) and E2F1
proteins with RecQL4 promoter suggests that Rb-E2F1 pathway may regulate RecQL4 expression. Collectively, our study shows that RecQL4 is an essential factor for prostate
carcinogenesis.