Gas6 Induces Proliferation in Prostate Carcinoma Cell Lines Expressing the Axl Receptor

J Cell Physiol. 2005 Jul;204(1):36-44. doi: 10.1002/jcp.20265.

Abstract

Axl is a tyrosine kinase receptor and although it is expressed in malignancy such as leukemia, colon cancer, melanoma, endometrial, prostate and thyroid cancers, its role has not been completely elucidated yet and appears to be complex. The ligand of Axl, Gas6, is a 75 KDa multimodular protein with an N-terminal gamma-carboxy-glutamic acid that is essential for binding. Gas6 has a mitogenic effect on several normal cell lines. The receptor Axl is expressed in primary prostate carcinoma and in prostate cancer cell lines as such as PC-3 and DU 145. We demonstrated a mitogenic activity determined by Gas6/Axl interaction in these undifferentiated metastatic human prostatic cancer cell lines. This effect is proportional to Axl expression, not due to inhibition of apoptosis, and induces AKT and MAPK phosphorylation. However, only MEK phosphorylation seems to be essential for growth signaling. Our results suggest that Axl overexpression and activation by Gas6 could be involved in progression of prostate neoplastic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Division
  • Cell Line, Tumor
  • Culture Media, Serum-Free / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • MAP Kinase Signaling System / physiology*
  • Male
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Prostatic Neoplasms / physiopathology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism

Substances

  • Culture Media, Serum-Free
  • Intercellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • growth arrest-specific protein 6
  • Phosphatidylinositol 3-Kinases
  • Receptor Protein-Tyrosine Kinases
  • axl receptor tyrosine kinase
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt