Growth arrest-specific gene 6 expression in human breast cancer.
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.
Mc Cormack
O
O
UCD School of Medicine and Medical Science, UCD Conway Institute, Belfield, Dublin 4, Ireland.
Chung
W Y
WY
Fitzpatrick
P
P
Cooke
F
F
Flynn
B
B
Harrison
M
M
Fox
E
E
Gallagher
E
E
Goldrick
A Mc
AM
Dervan
P A
PA
Mc Cann
A
A
Kerin
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D016019:Survival Analysis; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D000099255:Growth Arrest-Specific Protein 6; C097314:progesterone receptor B