ESTROGEN-RECEPTOR MESSENGER-RNA SPLICE VARIANTS IN PREMENOPAUSAL AND POSTMENOPAUSAL HUMAN ENDOMETRIUM AND ENDOMETRIAL CARCINOMA

Breast cancer tissue has been shown to contain alternatively spliced e strogen receptor (ER) mRNA variants which may result in alternate ER p roteins. These ER variants lack specific functional domains and may al ter breast cancer cells responses to both estrogen and antiestrogens. Specifically, ER variants might play a role in Tamoxifen resistance in breast cancer patients, as well as the development of endometrial car cinoma, an estrogen-dependent tumor, in patients taking this medicatio n. We investigated the presence of ER variants in normal human endomet rium and endometrial carcinoma. Ribonuclease protection assays (RPA) d emonstrated ER mRNA variants in the DNA and hormone-binding domains, T he reverse transcription-polymerase chain reaction (RT-PCR) assay was used to examine the ER complementary DNA (cDNA) from 25 patients, and generated two major products in both the exon 2 to 5 and 4 to 8 region s. Southern blot analysis of PCR products revealed exon 4 and 7 deleti ons in all 25 endometria without any qualitative differences in varian t expression among premenopausal, postmenopausal, and adenocarcinoma s amples. Cloning and sequencing of cDNA variants definitively identifie d exact deletions of either exon 4 or exon 7. These results demonstrat e significant levels of ER mRNA splice variants as well as full-length ER mRNA in normal and neoplastic endometria. (C) 1997 Academic Press.