HE4 (WFDC2) promotes tumor growth in endometrial cancer cell lines

Jinping Li, Haibin Chen, Andrea Mariani, Dong Chen, Edward Klatt, Karl Podratz, Ronny Drapkin, Russell Broaddus, Sean Dowdy, Shi Wen Jiang

Research output: Contribution to journalArticle

39 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6026-6043
Number of pages18
JournalInternational journal of molecular sciences
Issue number3
StatePublished - Mar 2013


  • Colony formation
  • Endometrial cancer
  • HE4 variant
  • Human epididymis protein 4 (HE4)
  • Invasion
  • Proliferation
  • Tumorigenesis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Li, J., Chen, H., Mariani, A., Chen, D., Klatt, E., Podratz, K., Drapkin, R., Broaddus, R., Dowdy, S., & Jiang, S. W. (2013). HE4 (WFDC2) promotes tumor growth in endometrial cancer cell lines. International journal of molecular sciences, 14(3), 6026-6043. https://doi.org/10.3390/ijms14036026