Abstract
Activation of Rac by guanine‐nucleotide exchange factors (GEFs) has been suggested to play an important role in cell migration which is critical for tumor metastasis. Here we investigated the role of P‐Rex1, a novel specific GEF for Rac, in human prostate cancer cell migration. PCR and immunofluorescent staining showed that the expression of P‐Rex1 was undetectable in normal prostate epithelial cells (PrEC) and less metastatic LNCaP cells but significantly increased in more metastatic prostate cancer cell lines (DU‐145, PC‐3‐LN4 and PC‐3). Our study also revealed increased P‐Rex1 protein level in human prostate tumor specimens compared to the corresponding normal prostate tissues. Using an in vitro transwell migration chamber assay, we found that NIH‐3T3 conditioned media (3T3‐CM) can induce prostate cancer cell migration which positively correlates with expression levels of P‐Rex1. Exogenously expressed P‐Rex1 enhanced Gi‐coupled receptor‐dependent migration of PC‐3‐LN4 cells up to four‐fold in a dose‐dependent manner. Knockdown of endogenous P‐Rex1 by small interfering RNA reduced the migration of PC‐3 cells. Furthermore, exogenous expression of P‐Rex1 in PC‐3‐LN4 cells induced strong Rac‐dependent lamellipodia. Our results suggest that up‐regulation of P‐Rex1 promotes prostate cancer cell migration and contributes to the metastasis of prostate cancer. (The Nebraska State LB595 to Y. Tu.)