R. Sager et al., IDENTIFICATION BY DIFFERENTIAL DISPLAY OF ALPHA-6 INTEGRIN AS A CANDIDATE TUMOR-SUPPRESSOR GENE, The FASEB journal, 7(10), 1993, pp. 964-970
A new method of differential expression cloning called differential di
splay (DD) has been used to screen for novel tumor suppressor genes in
volved in breast cancer. The screen is based on positive selection at
the mRNA level for genes expressed in normal mammary epithelial cells
but decreased or lost in corresponding tumor cells. A candidate tumor
suppressor gene recovered by DD is integrin alpha-6 (alpha6), a compon
ent of the heterodimeric integrin receptors alpha6beta1 and alpha6beta
4. Loss of alpha6 expression was confirmed in total RNAs by Northern b
lot analysis and by immunostaining with alpha6 antibodies. Consistent
with these cell culture findings, previous immunostaining of mammary t
issue sections has identified decreased alpha6 protein expression duri
ng breast tumor progression. Southern blot analysis demonstrated that
alpha6 gene is present in tumor cell lines, suggesting that re-express
ion may be inducible by pharmacological intervention. The likelihood t
hat alpha6 may have tumor suppressing activity is supported by growing
evidence of a central role for integrins in transducing growth contro
l and differentiation signals from growth factors and the extracellula
r matrix (ECM).