Links between Fer tyrosine kinase expression levels and prostate cell proliferation

Mol Cell Endocrinol. 2000 Jan 25;159(1-2):63-77. doi: 10.1016/s0303-7207(99)00205-1.


In our cloning strategy to identify tyrosine kinases implicated in the regulation of prostate growth, the dog fer cDNA was obtained and shown to be highly homologous to known fer cDNAs. Using a polyclonal Fer antibody directed against a C-terminal peptide, we studied its associations with cortactin, beta-catenin and p120Cas in human prostate carcinoma PC-3 cells. In contrast to previous reports, no interactions were observed. To assess its functional role, fer cDNA constructs were transfected in PC-3 cells. Antisense clones exhibiting a marked diminution of Fer expression had a reduced growth rate (doubling time of 29 vs. 42 h) and were unable to form colonies in soft 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 and LNCaP. In the dog model, Fer expression was up-regulated in dividing versus 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 androgens. Taken together, these results show that Fer expression is associated with prostate cell proliferation and enhanced in prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies
  • Base Sequence
  • Cell Division
  • Cloning, Molecular
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Dogs
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Male
  • Molecular Sequence Data
  • Prostate / cytology*
  • Prostate / enzymology*
  • Prostatic Hyperplasia / enzymology
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Transfection
  • Tumor Cells, Cultured


  • Antibodies
  • DNA Primers
  • DNA, Complementary
  • Proto-Oncogene Proteins
  • proto-oncogene protein c-fes-fps
  • Protein-Tyrosine Kinases