An Estrogen Receptor β Isoform That Lacks Exon 5 Has Dominant Negative Activity on both ERα and ERβ

Evaluation of mRNA expression of estrogen receptor β and its isoforms in human normal and neoplastic endometrium

“…3 We also examined an isoform of ER␤ that, in addition to changes in the C terminus, lacks exon 5 (ER␤2⌬5); it is missing a part of the LBD. 24,25,35 We have shown downregulation of the ER␤2⌬5 isoform in endometrial carcinoma. The significance of this finding may be explained by the work of Weihua et al, 32 who showed that when ER␤ is disabled (as in ER␤ knockout mice) there is an unusual proliferation of cells in the uterus.…”

“…Indeed, in transfection experiments, such truncated receptor proteins have been found to possess dominant negative activities. 25,33,34 We studied the expression of ER␤ isoforms with a truncation, insertion or exchange of sequences in the C-terminal/ LBD (ER␤1, ER␤2, ER␤3, ER␤4 and ER␤5) since they are the most frequently observed ER␤ isoforms in breast, ovarian, prostate and colon cancers. 7,20,22,23,[27][28][29][30] The predicted amino acid sequence of the above-mentioned isoforms diverges at amino acid 469 within the LBD (middle of helix 10 of LBD) and extends to the C terminus.…”

“…For example, ER␣, which lacks exon 5, has been associated with breast cancer, 23 as have the ER␤ isoforms ER␤2 (also named ER␤cx) and ER␤2⌬5. 24,25 This suggests that changes in transcript levels of the ER isoforms take place during tumorigenesis and are important both in etiology and in the assessment of cancer invasiveness.We evaluated the mRNA expression of all ER␤ isoforms (referred to as "total ER␤") and of ER␤1, ER␤2, ER␤2⌬5, ER␤3, ER␤4 and ER␤5 in normal and neoplastic endometrium. We refer our findings to histopathologic data (FIGO 1988 criteria 26 ) as well as to menstrual status.…”

“…For example, ER␣, which lacks exon 5, has been associated with breast cancer, 23 as have the ER␤ isoforms ER␤2 (also named ER␤cx) and ER␤2⌬5. 24,25 This suggests that changes in transcript levels of the ER isoforms take place during tumorigenesis and are important both in etiology and in the assessment of cancer invasiveness.…”

Oestrogen receptor β and neoadjuvant therapy with tamoxifen: prediction of response and effects of treatment

“…The situation is complicated further by the identification of a number of splice variant isoforms of the human ERb gene (Moore et al, 1998), the mRNAs for which have been detected in breast cancer tissues and breast cancer cell lines (Fuqua et al, 1999;Speirs et al, 2000;Poola et al, 2002a, b). Studies in vitro have suggested that ERb isoforms with deletions of selected exons, or with alternative splicing at the C-terminus, may act as dominant-negative inhibitors of full-length ERa and/or ERb (Ogawa et al, 1998b;Inoue et al, 2000;Peng et al, 2003).…”