ESTROGEN RECEPTOR α VARIANT PROTEIN LACKING THE HORMONEBINDING PERSISTS IN HUMAN BREAST CANCER

Abstract

Estrogen receptor alpha (ERα) variant proteins lacking the hormone-binding domains translated from their splice variant mRNAs were examined by Western blot analysis of 80 cases of human breast cancer. Wild ERα protein (ERwtP) was expressed in 68 cases (85.0%), and of these cases, 40 (58.8%) co-expressed ERα variant protein corresponding in size to 41kDa (ERd5P). There was a significant correlation between co-expression of ERd5P and the splice variant mRNA lacking exon 5 (ERd5M) examined by reverse transcription-polymerase chain reaction. No protein bands for ERα variant corresponding in size to 52kDa (ERd7P) were observed in spite of the splice variant mRNA lacking exon 7 (ERd7M) being co-expressed with wild-type mRNA. Our results suggest that ERd5P persists and is stable in a large proportion of samples of human breast cancer tissue, whereas ERd7P is not. The functional difference between ERwtP and ERd5P has yet to be established, and its discovery may demonstrate the importance of ERd5P for anti-estrogen resistance in human breast cancer.