HE4 (WFDC2) gene overexpression promotes ovarian tumor growth

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

doi:10.1038/srep03574

Back

HE4 (WFDC2) gene overexpression promotes ovarian tumor growth

Journal article

Open access

Peer reviewed

HE4 (WFDC2) gene overexpression promotes ovarian tumor growth

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, …

Scientific reports, Vol.4(3574), pp.3574-3574

01/06/2014

DOI: 10.1038/srep03574

PMCID: PMC3880958

PMID: 24389815

Files and links (1)

url

https://doi.org/10.1038/srep03574View

Published (Version of record) Open Access

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.

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

Ovarian Neoplasms - drug therapy

Ovarian Neoplasms - pathology

Proteins - genetics

Proteins - metabolism

Details

Title: Subtitle: HE4 (WFDC2) gene overexpression promotes ovarian tumor growth
Creators: Richard G Moore - Brown University
Emily K Hill - Brown University
Timothy Horan - Brown University
Naohiro Yano - Brown University
KyuKwang Kim - Molecular Therapeutics Laboratory, Program in Women's Oncology, Women and Infants' Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02903, USA
Shannon MacLaughlan - Stanford School of Medicine, Gynecology Oncology, Stanford, USA
Geralyn Lambert-Messerlian - Brown University
YiTang Don Tseng - Brown University
James F Padbury - Brown University
M Craig Miller - Brown University
Thilo S Lange - Brown University
Rakesh K Singh - Brown University
Resource Type: Journal article
Publication Details: Scientific reports, Vol.4(3574), pp.3574-3574
DOI: 10.1038/srep03574
PMID: 24389815
PMCID: PMC3880958
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: R01 CA136491 / NCI NIH HHS R01 CA136491-01 / NCI NIH HHS
Language: English
Date published: 01/06/2014
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9984318227502771

Metrics

14 Record Views

73 Times Cited - Web of Science

See more details