Expression of ERα, its ERαΔ3 Splice Variant and γ-SYNUCLEIN in Ovarian Cancer: A Pilot Study
Karen T. Cheung, Siân E. Taylor, Imran I. Patel, Adam J. Bentley, Helen F. Stringfellow, Nigel J. Fullwood, Pierre L. Martin-Hirsch, Francis L. Martin
Journal of Advances in Medicine and Medical Research · pp. 430–444 · Published 14 Sep 2011
10.9734/BJMMR/2011/769Abstract
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.
Cited by 11
Zhang J, Liu XH, Li C · J Exp Clin Cancer Res · 2020
Strohl A, Mori K, Akers S · J Ovarian Res · 2016
Panneerselvam M, Muthu K, Ramadas K. · Mol Biosyst · 2015
Panneerselvam M, Muthu K, Jayaraman M · Mol Biosyst · 2013
Gajjar K, Martin-Hirsch PL, Martin FL. · Cancer Lett · 2012
S. MacLean, W. S. Khan, A. A. Malik · Stem Cells International · 2012
Manivel Panneerselvam, Kannan Muthu, Muthukumaran Jayaraman · Molecular BioSystems · 2013
Jing Zhang, Xiao-han Liu, Cong Li · Journal of Experimental & Clinical Cancer Research · 2020
Ketan Gajjar, Pierre L. Martin-Hirsch, Francis L. Martin · Cancer Letters · 2012
Anna Strohl, Kristina Mori, Stacey Akers · Journal of Ovarian Research · 2016
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