Gene Expression Analyses Support Fallopian Tube Epithelium as the Cell of Origin of Epithelial Ovarian Cancer

International Journal of Molecular Sciences

Daniel J. O’Shannessy¹  Stephen M. Jackson¹  Natalie C. Twine²  Bryan E. Hoffman¹  Zoltan Dezso²  Sergei I. Agoulnik² 

[1] Department of Translational Medicine and Diagnostics, Morphotek, Inc., 210 Welsh Pool Rd., Exton, PA 19341, USA; E-Mails:;Biomarkers and Personalized Medicine Core Functional Unit, Eisai Inc., Four Corporate Drive, Andover, MA 01810,USA; E-Mails:

关键词: folate receptor alpha;    FRA;    ovarian cancer;    fallopian tube;    1-carbon metabolism;    reduced folate carrier;    methylation;   

DOI  :  10.3390/ijms140713687

来源: mdpi

【 摘 要 】

Folate receptor alpha (FOLR1/FRA) is reported to be overexpressed in epithelial ovarian cancers (EOC), especially the serous histotype. Further, while dysregulation of the folate-dependent 1-carbon cycle has been implicated in tumorogenesis, little is known relative to the potential mechanism of action of FOLR1 expression in these processes. We therefore investigated the expression of FOLR1, other folate receptors, and genes within the 1-carbon cycle in samples of EOC, normal ovary and fallopian tube on a custom TaqMan Low Density Array. Also included on this array were known markers of EOC such as MSLN, MUC16 and HE4. While few differences were observed in the expression profiles of genes in the 1-carbon cycle, genes previously considered to be overexpressed in EOC (e.g., FOLR1, MSLN, MUC16 and HE4) showed significantly increased expression when comparing EOC to normal ovary. However, when the comparator was changed to normal fallopian tube, these differences were abolished, supporting the hypothesis that EOC derives from fallopian fimbriae and, further, that markers previously considered to be upregulated or overexpressed in EOC are most likely not of ovarian origin, but fallopian in derivation. Our findings therefore support the hypothesis that the cell of origin of EOC is tubal epithelium.

【 授权许可】

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© 2013 by the authors; licensee MDPI, Basel, Switzerland