Identification of novel transcript variants of estrogen receptor α, β and progesterone receptor gene in human endometrium.
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 ERα, four single, double or triple exon-skipped mRNA isoforms of ERβ, and four new transcript variations of PR gene. Sequence analysis suggested that at least four of them, ERαΔ5/6, ERαΔ5/6/7, PRΔ7, and PRΔ6/7 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 PRΔ6/7, ERαΔ5/6/7, ERαΔ3/4/5, and ERβΔ1-0N. 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.
Department of Obstetrics and Gynecology, University Medical Center Regensburg, Regensburg, Germany.
Anette
A
Springwald
Claus
C
Lattrich
Maciek
M
Skrzypczak
Regina
R
Goerse
Olaf
O
Ortmann
Oliver
O
Treeck
D017398:Alternative Splicing; D004717:Endometrium / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011980:Receptors, Progesterone