Growth arrest-specific gene 6 expression in human breast cancer

Abstract

Growth arrest- specific gene 6 ( Gas6), identified in 1995, acts as the ligand to the Axl/ Tyro3 family of tyrosine kinase receptors and exerts mitogenic activity when bound to these receptors. Overexpression of the Axl/ Tyro3 receptor family has been found in breast, ovarian and lung tumours. Gas6 is upregulated 23- fold by progesterone acting through the progesterone receptor B ( PRB). Recently, Gas6 has been shown to be a target for overexpression and amplification in breast cancer. Quantitative real- time PCR analysis was used to determine the levels of Gas6 mRNA expression in 49 primary breast carcinomas. Expression of PRB protein was evaluated immunohistochemically with a commercially available PRB antibody. The results showed a positive association between PRB protein and Gas6 mRNA levels ( P =0.04). Gas6 correlated positively with a number of favourable prognostic variables including lymph node negativity ( P =0.0002), younger age at diagnosis ( P =0.04), smaller size of tumours ( P =0.02), low Nottingham prognostic index scores ( P =0.03) and low nuclear morphology ( P =0.03). This study verifies for the first time the association between PRB and Gas6 in breast cancer tissue.