Androgen receptor mutation in breast cancer

Normal breast growth and development depends on functional androgen:estrogen (A:E) balance. Androgen actions are mediated by the androgen receptor (AR), a DNA-binding, transcriptional-regulatory protein. Decreased AR transactivational. activity lowers A:E balance and may result in functional hyperestrogenicity: this could promote the pathogenesis of breast cancer (BC). The present study is the first to seek AR mutations in female BC. The length of the polymorphic CAG-repeat in exon 1 of the AR correlates inversely with the transactivational activity of the AR. Using 10% polyacrylamide gels, I found a significant (p < 0.0001) shift to greater CAG-repeat lengths in BC samples. This suggests a role for ARs with long polyglutamine tracts in the initiation and/or progression of BC. Exons 2--8 of the AR in 81 fresh frozen BC tumor tissues were screened for mutations using SSCP analysis. I did not detect any mutations in these exons