IDENTIFICATION BY DIFFERENTIAL DISPLAY OF ALPHA-6 INTEGRIN AS A CANDIDATE TUMOR-SUPPRESSOR GENE

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).