COEXPRESSION OF MULTIPLE ESTROGEN-RECEPTOR VARIANT MESSENGER-RNAS IN NORMAL AND NEOPLASTIC BREAST TISSUES AND IN MCF-7 CELLS

Mammary cancers often develop into a hormone-independent and antagonis t-resistant growth phase. The molecular mechanisms of this transition are not clear. Recently, it has been proposed that estrogen receptor v ariants derived from alternative splicing might lead to dominant posit ive transcription factors acting on estrogen response elements, even i n 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 surge ry. Variants are identified by reverse transcription PCR and hybridiza tion to exon-specific oligonucleotide probes. In MCF-7 cells we detect ed 10 variants including 5 that have not been described before. Skippi ng one, two, or three exons occurs, The major variants detected in the cell line are also present in normal and neoplastic tissues. Quantita tive variations allow no conclusions of a potential involvement of the variants in neoplastic processes. Rather, the variants appear to be p resent normally and thus might have a physiological role. Given the ex pression of the variants in normal tissue, and given the expression of potentially dominant positive variants in conjunction with potentiall y dominant negative ones, we suggest that these variants do not accoun t for hormone antagonist resistance.