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Int. J. Mol. Sci. 2013, 14(3), 6026-6043; doi:10.3390/ijms14036026

HE4 (WFDC2) Promotes Tumor Growth in Endometrial Cancer Cell Lines

1 Department of Biomedical Science, School of Medicine, Mercer University, Savannah, GA 31404, USA 2 Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN 55905, USA 3 Curtis and Elizabeth Anderson Cancer Institute, Department of Laboratory Oncology Research, Memorial University Medical Center, Savannah, GA 31404, USA 4 Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, Guangdong, China 5 Department of Pathology, Mayo Clinic Medical College, Rochester, MN 55905, USA 6 Department of Pathology, Harvard Medical School, Boston, MA 77030, USA 7 Department of Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 22 January 2013 / Revised: 7 February 2013 / Accepted: 25 February 2013 / Published: 15 March 2013
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
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HE4, also known as WFDC2, is a useful biomarker for ovarian cancer when either used alone or in combination with CA125. HE4 is also overexpressed in endometrial cancer (EC), but its function in cancer cells is not clear. In this study, we investigate the role of HE4 in EC progression. An HE4-overexpression system was established by cloning the HE4 prototypic mRNA variant (HE4-V0) into a eukaryotic expression vector. Following transfection, stable clones in two EC cell lines were selected. The effects of HE4 overexpression on cell growth and function were measured with the use of cell proliferation assay, matrigel invasion, and soft agar gel colony formation assays. HE4-induced cancer cell proliferation in vivo was examined in a mouse xenograft model. HE4 overexpression significantly enhanced EC cell proliferation, matrigel invasion, and colony formation in soft agar. Moreover, HE4 overexpression promoted tumor growth in the mouse xenograft model. HE4 overexpression enhanced several malignant phenotypes in cell culture and in a mouse model. These results are consistent with our previous observation that high levels of serum HE4 closely correlate with the stage, myometrial invasion and tumor size in patients with EC. This study provides evidence that HE4 overexpression directly impacts tumor progression in endometrial cancer.
Keywords: endometrial cancer; human epididymis protein 4 (HE4); HE4 variant; proliferation; invasion; colony formation; tumorigenesis endometrial cancer; human epididymis protein 4 (HE4); HE4 variant; proliferation; invasion; colony formation; tumorigenesis
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Li, J.; Chen, H.; Mariani, A.; Chen, D.; Klatt, E.; Podratz, K.; Drapkin, R.; Broaddus, R.; Dowdy, S.; Jiang, S.-W. HE4 (WFDC2) Promotes Tumor Growth in Endometrial Cancer Cell Lines. Int. J. Mol. Sci. 2013, 14, 6026-6043.

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