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 ¼ 0.04). Gas6 correlated positively with a number of favourable prognostic variables including lymph node negativity (P ¼ 0.0002), younger age at diagnosis (P ¼ 0.04), smaller size of tumours (P ¼ 0.02), low Nottingham prognostic index scores (P ¼ 0.03) and low nuclear morphology (P ¼ 0.03). This study verifies for the first time the association between PRB and Gas6 in breast cancer tissue.

Axl Phosphorylates Elmo Scaffold Proteins To Promote Rac Activation and Cell Invasion

“…Similarly, the Axl ligand Gas6 has been shown to be a target for overexpression and amplification in breast cancer (59). However, some studies have shown that upregulation of Axl in breast cancer cells led to an increase in Axl activity independently of Gas6 binding, confirming the constitutive activation of Axl in these cells (25).…”

A genomic screen identifies TYRO3 as a MITF regulator in melanoma

“…Concomitant expression of GAS6 and TAM receptors have been discovered in certain cancers, including breast cancer (52) and glioma (24,39). The role of Protein S, a close relative of GAS6, as a TYRO3 ligand is less clear: human Protein S binds to and activates murine TYRO3 in vitro (53), bovine Protein S activates human TYRO3 (54,55), but human Protein S is not able to activate human TYRO3 (56).…”

Differential Expression of Axl and Gas6 in Renal Cell Carcinoma Reflecting Tumor Advancement and Survival

“…The positive effects of high tumor Gas6 mRNA, together with the contrary expression patterns of tumor Axl and Gas6 mRNA in RCC, are intriguing because it has been shown in human glioma that high tumor Axl and Gas6 mRNA levels indicated worse prognosis (24) and because of observations that Gas6 binding to Axl stimulates proliferation and survival (37)(38)(39). Thus far, increased Gas6 mRNA correlating with favorable prognosis has only been reported in human breast cancer (40). Furthermore, in cRCC, tumor Axl mRNA levels were broadly distributed and the results are consequently more informative than those of a previous study of 20 patients that suggested Axl mRNA levels to be significantly up-regulated in cRCC (29).…”