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The ER?5 splice variant increases oestrogen responsiveness of ER?pos Ishikawa cells.

ABSTRACT: Endometrial cancer is a common gynaeological malignancy: life time exposure to oestrogen is a key risk factor. Oestrogen action is mediated by receptors encoded by ESR1 (ER?) and ESR2 (ER?): ER? plays a key role in regulating endometrial cell proliferation. A truncated splice variant isoform (ER?5) encoded by ESR2 is highly expressed in cancers. This study explored whether ER?5 alters oestrogen responsiveness of endometrial epithelial cells. Immunhistochemistry profiling of human endometrial cancer tissue biopsies identified epithelial cells co-expressing ER?5 and ER? in stage I endometrial adenocarcinomas and post menopausal endometrium. Induced co-expression of ER?5 in ER?pos endometrial cancer cells (Ishikawa) significantly increased ligand-dependent activation of an ERE-luciferase reporter stimulated by either E2 or the ER?-selective agonist 1,3,5-(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) compared to untransfected cells. Fluorescence recovery after photobleaching (FRAP) analysis of tagged yellow fluorescent protein (YFP)-ER?5 transfected into Ishikawa cells revealed that incubation with E2 induced a transient reduction in intra-nuclear mobility characterised by punctate protein redistribution which phenocopied the behaviour of ER? following ligand activation with E2. In ER?neg MDA-MD-231 breast cancer cells there was no E2-dependent change in mobility of YFP-ER?5 and no activation of the ERE reporter in cells expressing ER?5. In conclusion, we demonstrate that ER?5 can act as heterodimeric partner to ER? in Ishikawa cells and increases their sensitivity to E2. We speculate that expression of ER?5 in endometrial epithelial cells may increase the risk of malignant transformation and suggest that immunostaining for ER?5 should be included in diagnostic assessment of women with early grade cancers.

SUBMITTER: Collins F

PROVIDER: S-EPMC6933808 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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The ERβ5 splice variant increases oestrogen responsiveness of ERαpos Ishikawa cells.

Collins Frances F Itani Nozomi N Esnal-Zufiaurre Arantza A Gibson Douglas A DA Fitzgerald Carol C Saunders Philippa T K PTK

Endocrine-related cancer 20200201 2

Endometrial cancer is a common gynaeological malignancy: life time exposure to oestrogen is a key risk factor. Oestrogen action is mediated by receptors encoded by ESR1 (ERα) and ESR2 (ERβ): ERα plays a key role in regulating endometrial cell proliferation. A truncated splice variant isoform (ERβ5) encoded by ESR2 is highly expressed in cancers. This study explored whether ERβ5 alters oestrogen responsiveness of endometrial epithelial cells. Immunhistochemistry profiling of human endometrial can ...[more]

PMID: 31778358

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The ER?5 splice variant increases oestrogen responsiveness of ER?pos Ishikawa cells.

Publications

The ERβ5 splice variant increases oestrogen responsiveness of ERαpos Ishikawa cells.

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