title: Expression of ERα, its ERαΔ3 Splice Variant and γ-SYNUCLEIN in Ovarian Cancer: A Pilot Study.
abstract: AIMS: Ovarian cancer has the highest mortality of any gynaecological malignancy; this is due to rapid peritoneal spread of tumour cells and neovascularization. Understanding the mechanisms underlying this is critical to developing early diagnostic or treatment strategies. We devised a pilot study to examine the role of γ-SYNUCLEIN (γ-SYN), oestrogen receptor (ER)α, and the splice variant ERαΔ3.  METHODOLOGY: With ethical approval, ovarian tissue was collected from patients (n=24) undergoing oopherectomy for non-ovarian pathology or primary surgery for suspected ovarian cancer. Quantitative gene expression analysis was employed for γ-SYN, ERα, and ERαΔ3. To identify the in situ localization, immunofluorescence for γ-syn was carried out.  RESULTS: Ovarian tumour tissue exhibited an elevated expression of γ-SYN and high-grade tumours had an elevated ERαΔ3:ERα ratio compared with benign tissue. The majority of previous studies point to the γ-syn protein being present in epithelial cells of high-grade disease. Our study supports this, but additionally we conclusively identify its presence in the endothelial cells of vasculature surrounding low-grade disease; immunofluorescence was strongest in the apical cells surrounding the lumen.  CONCLUSION: Our results demonstrate for the first time that there are readily-expressed levels of γ-SYN and ERαΔ3 in normal ovarian tissue and ovarian tumours. In high-grade disease, γ-syn and an elevated ERαΔ3:ERα ratio might confer metastatic potential to the tumourigenic cells and promote neoangiogenesis. Future in vitro studies might be necessary to delineate such a mechanism, which could potentially be the basis of early intervention.
authors.affiliation: Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Cheung
authors.forename: Siân E
authors.initials: SE
authors.lastname: Taylor
authors.forename: Imran I
authors.initials: II
authors.lastname: Patel
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bentley
authors.forename: Helen F
authors.initials: HF
authors.lastname: Stringfellow
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Fullwood
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Martin-Hirsch
authors.forename: Francis L
authors.initials: FL
authors.lastname: Martin
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