Expression of ZER6 in ERα-Positive Breast Cancer

Abstract

ZER6 is a C2H2 zinc finger transcription factor with two isoforms (p52-ZER6 and p71-ZER6), which are differentially repressed by a ligand-dependent interaction with estrogen receptor-alpha (ERalpha). We sought to determine if ZER6 proteins are expressed in ERalpha-positive breast cancer cells and if ZER6 is expressed in association with ERalpha in breast cancers. The expression of ZER6 protein was examined by Western blot and the pattern of ZER6 expression was examined in a panel of ERalpha-positive and ERalpha-negative breast cancers using RT-PCR. COS-1 cells transfected with expression vectors for p52-ZER6 express a major protein of 52 kDa and a minor protein of 75 kDa, whereas cells transfected with the p71-ZER6 expression vector express a major protein of 77 kDa and a minor protein of 100 kDa. Breast carcinoma cells express ZER6-specific proteins of similar size, and expression of the p52-ZER6 isoform was only detected in the ERalpha-positive cell lines. In primary breast cancer tissue, 8/16 (50%) of the ERalpha-positive tumors had high ZER6 expression, whereas only 1/12 (8%) of the ERalpha-negative tumors had a high ZER6 level of expression. The relative abundance of ZER6 mRNA in the ERalpha-positive group was statistically greater than the ERalpha-negative group (188 versus 106, P < 0.05). We have confirmed that breast carcinoma cells express ZER6 proteins and identified an association between the level of ZER6 expression and ERalpha expression in primary breast cancers. These data support a role for the ZER6 transcription factors in regulating the expression of genes in hormone-responsive breast cancer.