Growth arrest-specific gene 6 expression in human breast cancer

• Published in: British journal of cancer Vol. 98; no. 6; pp. 1141 - 1146
• Main Authors: Mc Cormack, O, Chung, W Y, Fitzpatrick, P, Cooke, F, Flynn, B, Harrison, M, Fox, E, Gallagher, E, Goldrick, A Mc, Dervan, P A, Mc Cann, A, Kerin, M J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.03.2008; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - genetics; Cancer Research; Disease-Free Survival; Drug Resistance; Epidemiology; Female; Gene Expression; Genetics and Genomics; Gynecology. Andrology. Obstetrics; Humans; Intercellular Signaling Peptides and Proteins - genetics; Mammary gland diseases; Medical sciences; Middle Aged; Molecular Medicine; Oncology; Polymerase Chain Reaction; Receptors, Progesterone - metabolism; Risk Factors; RNA, Messenger - analysis; Survival Analysis; Tumors; Axl tyrosine kinase receptor; breast cancer; progesterone receptor B; growth arrest-specific gene 6; Human; Breast disease; growth arrest-specific gene 6; Axl tyrosine kinase receptor; Growth; Receptor tyrosine kinase; Breast cancer; Malignant tumor; Gene expression; Progesterone receptor; Mammary gland diseases; Cancerology; Gene; progesterone receptor B; breast cancer; Genetics; Cancer; Hormonal receptor
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604260

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.