Links between Fer tyrosine kinase expression levels and prostate cell proliferation

In our cloning strategy to identify tyrosine kinases implicated in the regu lation of prostate growth, the dog fel cDNA was obtained and shown to be hi ghly homologous to known fer cDNAs, Using a polyclonal Fer antibody directe d against a C-terminal peptide, we studied its associations with cortactin, beta-catenin and p120Cas in human prostate carcinoma PC-3 cells. In contra st to previous reports, no interactions were observed. To assess its functi onal role, fer cDNA constructs were transfected in PC-3 cells. Antisense cl ones exhibiting a marked diminution of Per expression had a reduced growth rate (doubling time of 29 vs. 42 h) and were unable to form colonies in sof t agar. In agreement with these results, Fer protein expression was linked to human prostatic proliferative diseases, with enhanced levels in extracts from cancer tissues as compared to those from normal and hyperplastic ones , and was also expressed in the human prostate carcinoma cell lines DU145 a nd LNCaP. In the dog model, Fer expression was up-regulated in dividing ver sus resting prostate epithelial cells in vitro, and also in vivo when basal cell hyperplasia and metaplasia was induced by estrogen after castration. Minimal effects were observed when renewing the luminal epithelium with and rogens. Taken together, these results show that Fer expression is associate d with prostate cell proliferation and enhanced in prostate cancer. (C) 200 0 Elsevier Science Ireland Ltd. All rights reserved.