FOCAL ADHESION KINASE (PP125(FAK)) EXPRESSION, ACTIVATION AND ASSOCIATION WITH PAXILLIN AND P50(CSK) IN HUMAN METASTATIC PROSTATE CARCINOMA

pp125(FAK), a protein tyrosine kinase (PTK) co-localized with integrin s in focal adhesion plaques, is known to transduce signals involved in the regulation of cell adhesion and motility as well as the anchorage -independent growth of transformed cells. We investigated whether pp12 5(FAK) could be part of a signalling pathway that contributes to the p rogression of human prostate carcinoma (PCa). Up-regulation of pp125(F AK) expression, its activation by phosphorylation on tyrosine and its association with paxillin and p50(csk) were preferentially observed in PCa tissues from patients with metastases, whereas normal and hyperpl astic prostates and localized PCa tissues showed undetectable or low l evels of both FAK mRNA and protein and an absence of pp125(FAK) Signal ling complexes. The increase in expression and activation of pp125(FAK ) in metastatic PCa tissues was also corroborated by our findings in h uman PCa cell lines. Indeed, higher levels of pp125(FAK) and FAK mRNA were observed in highly tumorigenic PC-3 cells as was the presence of activated pp125(FAK), as opposed to an inactive form in LNCaP cells, w hich have a lower tumorigenic ability. In addition, pp125(FAK) formed signalling complexes with both paxillin and p50(csk) in PC-3 cells as in metastatic PCa tissues. Together, our results show that an increase in FAK mRNA and protein, as well as pp125(FAK) activation and associa tion with signalling proteins, correlates with progression and invasio n in human PCa tissues and cells. (C) 1996 Wiley-Liss, Inc.