Gas6 induces proliferation in prostate carcinoma cell lines expressing the Axl receptor

AxI 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 AxI, 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 AxI 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 AxI 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 AxI overexpression and activation by Gas6 could be involved in progression of prostate neoplastic disease.