HE4 (WFDC2) gene overexpression promotes ovarian tumor growth.

Abstract

Selective overexpression of Human epididymal secretory protein E4 (HE4) points to a role in ovarian cancer tumorigenesis but little is known about the role the HE4 gene or the gene product plays. Here we show that elevated HE4 serum levels correlate with chemoresistance and decreased survival rates in EOC patients. HE4 overexpression promoted xenograft tumor growth and chemoresistance against cisplatin in an animal model resulting in reduced survival rates. HE4 displayed responses to tumor microenvironment constituents and presented increased expression as well as nuclear translocation upon EGF, VEGF and Insulin treatment and nucleolar localization with Insulin treatment. HE4 interacts with EGFR, IGF1R, and transcription factor HIF1α. Constructs of antisense phosphorothio-oligonucleotides targeting HE4 arrested tumor growth in nude mice. Collectively these findings implicate increased HE4 expression as a molecular factor in ovarian cancer tumorigenesis. Selective targeting directed towards the HE4 protein demonstrates therapeutic benefits for the treatment of ovarian cancer.

• Authors: Richard G Moore, Emily K Hill, Timothy Horan, Naohiro Yano, KyuKwang Kim, Shannon MacLaughlan, Geralyn Lambert-Messerlian, YiTang Don Tseng, James F Padbury, M Craig Miller, Thilo S Lange, Rakesh K Singh
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 3574 (Jan 06 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24389815 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Proteins
• WAP Four-Disulfide Core Domain Protein 2
• WFDC2 protein, human
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Cell Division (genetics)
• Cisplatin (therapeutic use)
• Disease Models, Animal
• Drug Resistance, Neoplasm
• Female
• Gene Expression
• Humans
• Mice
• Ovarian Neoplasms (blood, drug therapy, pathology)
• Proteins (genetics, metabolism)
• WAP Four-Disulfide Core Domain Protein 2