Coexpression of multiple estrogen receptor variant messenger RNAs in normal and neoplastic breast tissues and in...

Mammary cancers often develop into a hormone-independent and antagonist-resistant growth phase. The molecular mechanisms of this transition are not clear. Recently, it has been proposed that estrogen receptor variants derived from alternative splicing might lead to dominant positive transcription factors acting on estrogen response elements, even in the absence of the hormone. We show here the comprehensive analysis of expression of estrogen receptor variants lacking internal exons in the estrogen receptor-positive mammary carcinoma cell line MCF-7, in a tumor sample, and in healthy breast tissue taken from reduction surgery. Variants are identified by reverse transcription PCR and hybridization to exon-specific oligonucleotide probes. In MCF-7 cells we detected 10 variants including 5 that have not been described before. Skipping one, two, or three exons occurs. The major variants detected in the cell line are also present in normal and neoplastic tissues. Quantitative variations allow no conclusions of a potential involvement of the variants in neoplastic processes. Rather, the variants appear to be present normally and thus might have a physiological role. Given the expression of the variants in normal tissue, and given the expression of potentially dominant positive variants in conjunction with potentially dominant negative ones, we suggest that these variants do not account for hormone antagonist resistance.