Stabach Paul R, Thiyagarajan Manimekalai M, Weigel Ronald J
Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
J Surg Res. 2005 Jun 1;126(1):86-91; discussion 1-2. doi: 10.1016/j.jss.2005.02.006.
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.
ZER6是一种C2H2锌指转录因子，有两种异构体（p52-ZER6和p71-ZER6），它们通过与雌激素受体α（ERα）的配体依赖性相互作用受到不同程度的抑制。我们试图确定ZER6蛋白是否在ERα阳性乳腺癌细胞中表达，以及ZER6是否在乳腺癌中与ERα共同表达。
通过蛋白质免疫印迹法检测ZER6蛋白的表达，并使用逆转录聚合酶链反应（RT-PCR）检测一组ERα阳性和ERα阴性乳腺癌中ZER6的表达模式。
用p52-ZER6表达载体转染的COS-1细胞表达一种主要的52 kDa蛋白和一种次要的75 kDa蛋白，而用p71-ZER6表达载体转染的细胞表达一种主要的77 kDa蛋白和一种次要的100 kDa蛋白。乳腺癌细胞表达大小相似的ZER6特异性蛋白，并且仅在ERα阳性细胞系中检测到p52-ZER6异构体的表达。在原发性乳腺癌组织中，16例ERα阳性肿瘤中有8例（50%）ZER6高表达，而12例ERα阴性肿瘤中只有1例（8%）ZER6表达水平高。ERα阳性组中ZER6 mRNA的相对丰度在统计学上高于ERα阴性组（188对106，P < 0.05）。
我们已经证实乳腺癌细胞表达ZER6蛋白，并确定了原发性乳腺癌中ZER6表达水平与ERα表达之间的关联。这些数据支持ZER6转录因子在调节激素反应性乳腺癌基因表达中的作用。
