WAVE3 is associated with invasiveness in prostate cancer cells

Introduction: Wiskott-Aldrich syndrome verprolin-homologous 3 (WAVE3) belongs to Wiskott-Aldrich syndrome family proteins (WASP), which, along with other members, play a critical role in the regulation of actin polymerization and cell motility. We investigated the expression pattern and the effects of manipulating endogenous WAVE3 expression in prostate cancer cells. Materials and methods: Reverse transcriptase-polymerase chain reaction (RT-PCR) of prostate cell lines and immunohistochemical staining of normal and cancer specimens for WAVE3 proteins were done. WAVE3 knockdown clones were synthesized using hammerhead ribozyme transgenes and transfected by electroporation into DU-145 and PC-3 cells. The impact of WAVE3 knockdown was studied using in vitro functional assays. Results: RT-PCR for WAVE3 showed strong expression in both PC-3 and DU-145 cell lines. Immunohistochemistry of prostate tissue specimens showed that the cytoplasm of cancer cells had stronger staining than normal epithelium. The mean [(+/-standard error of mean (SEM)] invading cell number for PC-3(Delta W3R1) and PC-3(Delta W3R2) was 5.06 (+/-0.42) and 6.33 (+/-0.19), respectively, compared with PC-3(WT) (12.27 +/- 0.42; P < 0.001). Similarly, the mean (+/-SEM) invading cell numbers for DU-145(Delta W3R1) and DU-145(Delta W3R2) were 10.80 (+/-1.33) and 10.20 (+/-0.86) compared with DU-145(WT) (14.80 +/- 0.24, P < 0.05). No significant differences were observed in the adhesiveness and proliferation between the knockdown mutants and the wild types. Conclusions: This is the first report on the expression patterns and the functions of WAVE3 in prostate cancer cell lines. This study shows that WAVE3 is pivotal in controlling the invasiveness of prostate cancer cells. Further work is needed to assess WAVE3 as a potential marker for predicting tumor aggressiveness. (C) 2010 Elsevier Inc. All rights reserved.