Abstract
The human progesterone receptor (PR) and estrogen receptor genes (ESR1 and ESR2) are known to code for a multitude of transcript variants resulting from alternative splicing. Many of them are translated into nuclear receptor proteins with altered structure and function. Expression of these alternative estrogen and progesterone receptors modulates the cellular response to sexual steroid hormones. ...
Abstract
The human progesterone receptor (PR) and estrogen receptor genes (ESR1 and ESR2) are known to code for a multitude of transcript variants resulting from alternative splicing. Many of them are translated into nuclear receptor proteins with altered structure and function. Expression of these alternative estrogen and progesterone receptors modulates the cellular response to sexual steroid hormones. Recent studies also suggested their significance in development of hormone-dependent diseases like gynecological cancers. We report identification of 12 new transcript variations of the PR, ESR1, and ESR2 gene in human endometrium which result from differential exon-skipping. We succeeded in cloning of four new double or triple exon-deletion transcript variants of ER alpha, four single, double or triple exon-skipped mRNA isoforms of ER beta, and four new transcript variations of PR gene. Sequence analysis suggested that at least four of them, ER alpha I"5/6, ER alpha I"5/6/7, PR Delta 7, and PR Delta 6/7 are translated into receptor proteins which might exert ligand-independent effects on steroid hormone signalling. Comparison of pre- and post-menopausal endometrium revealed differential expression of PR Delta 6/7, ER alpha I"5/6/7, ER alpha I"3/4/5, and ER beta I"1-0N. We also report differential expression of the exon-skipped isoforms in a panel of human cancer cell lines derived from the breast, ovary, and endometrium. Our identification of additional transcript variations further increases the complexity of steroid hormone receptor gene expression and signalling.
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