Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
January-2015 Volume 33 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2015 Volume 33 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

  • Authors:
    • Huan Wang
    • Liancheng Zhu
    • Jian Gao
    • Zhenhua Hu
    • Bei Lin
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Heping, Shenyang, Liaoning 110004, P.R. China
  • Pages: 403-412
    |
    Published online on: October 17, 2014
       https://doi.org/10.3892/or.2014.3549
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Available evidence on the proliferation-promoting effect of HE4 remains controversial, and few studies have been carried out on the molecular mechanism of chemoresistance mediated by HE4. The aim of the present study was to investigate the influence of exogenous recombinant HE4 protein on proliferation and resistance to carboplatin in ovarian cancer cells. The human ovarian cancer cell line (SKOV-3) was exposed to recombinant HE4 protein (0-1 µg/ml) for different durations based on the schemes. Cell viability was evaluated by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Markers of apoptosis (Bax and Bcl-2) were assessed by western blotting. Furthermore, Affymetrix microarray analysis was performed to investigate transcriptome profiling. The differential expression of four genes was verified by quantitative real-time PCR. The HE4 protein enhanced cell viability, promoted accumulation of cells in the G2/M phase and attenuated carboplatin-induced apoptosis. HE4 markedly decreased the Bax/Bcl-2 ratio. Candidate genes (387) (236 upregulated and 151 downregulated) were obtained by microarray analysis. Among those upregulated, several Gene Ontology (GO) terms related to cell cycle regulation and proliferation were significantly overrepresented and those within the downregulated dataset included genes involved in several aspects of the DNA damage response such as positive regulation of apoptosis. No information concerning the EGFR-MAPK pathways in a recent report on HE4 was acquired. The mRNA expression of the candidate genes determined by quantitative real-time PCR was significantly correlated with the microarray data. The present study indicates that the HE4 protein plays a promotive role in the proliferation and resistance to carboplatin in ovarian cancer cells, implicating the value of HE4 to predict tumor growth potential and resistance to platinum-based chemotherapy in epithelial ovarian cancer (EOC).
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Kirchhoff C, Habben I, Ivell R and Krull N: A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod. 45:350–357. 1991. View Article : Google Scholar : PubMed/NCBI

2 

Kirchhoff C: Molecular characterization of epididymal proteins. Rev Reprod. 3:86–95. 1998. View Article : Google Scholar : PubMed/NCBI

3 

Clauss A, Lilja H and Lundwall A: A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein. Biochem J. 368:233–242. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Williams SE, Brown TI, Roghanian A and Sallenave JM: SLPI and elafin: one glove, many fingers. Clin Sci. 110:21–35. 2006. View Article : Google Scholar

5 

Moreau T, Baranger K, Dadé S, Dallet-Choisy S, Guyot N and Zani ML: Multifaceted roles of human elafin and secretory leukocyte proteinase inhibitor (SLPI), two serine protease inhibitors of the chelonianin family. Biochimie. 90:284–295. 2008. View Article : Google Scholar

6 

Tanner MM, Grenman S, Koul A, et al: Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res. 6:1833–1839. 2000.PubMed/NCBI

7 

Larramendy ML, Lushnikova T, Björkqvist AM, et al: Comparative genomic hybridization reveals complex genetic changes in primary breast cancer tumors and their cell lines. Cancer Genet Cytogenet. 119:132–138. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Hoskins E, Rodriguez-Canales J, Hewitt SM, et al: Paracrine SLPI secretion upregulates MMP-9 transcription and secretion in ovarian cancer cells. Gynecol Oncol. 122:656–662. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Sonoda G, Palazzo J, du Manoir S, et al: Comparative genomic hybridization detects frequent overrepresentation of chromosomal material from 3q26, 8q24, and 20q13 in human ovarian carcinomas. Genes Chromosomes Cancer. 20:320–328. 1997. View Article : Google Scholar : PubMed/NCBI

10 

Kiechle M, Jacobsen A, Schwarz-Boeger U, Hedderich J, Pfisterer J and Arnold N: Comparative genomic hybridization detects genetic imbalances in primary ovarian carcinomas as correlated with grade of differentiation. Cancer. 91:534–540. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Iwabuchi H, Sakamoto M, Sakunaga H, et al: Genetic analysis of benign, low-grade, and high-grade ovarian tumors. Cancer Res. 55:6172–6180. 1995.PubMed/NCBI

12 

Idoji Y, Watanabe Y, Yamashita A, et al: In silico study of whey-acidic-protein domain containing oral protease inhibitors. Int J Mol Med. 21:461–468. 2008.PubMed/NCBI

13 

LeBleu VS, Teng Y, O’Connell JT, et al: Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis. Nat Med. 19:227–231. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Drapkin R, von Horsten HH, Lin Y, et al: Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 65:2162–2169. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Galgano MT, Hampton GM and Frierson HF Jr: Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol. 19:847–853. 2006.PubMed/NCBI

16 

Schummer M, Ng WV, Bumgarner RE, et al: Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene. 238:375–385. 1999. View Article : Google Scholar : PubMed/NCBI

17 

Zanotti L, Bignotti E, Calza S, et al: Human epididymis protein 4 as a serum marker for diagnosis of endometrial carcinoma and prediction of clinical outcome. Clin Chem Lab Med. 50:2189–2198. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Tokuishi K, Yamashita S, Ohbo K and Kawahara K: Splice variant HE4-V3 expression is associated with favorable prognosis in pulmonary adenocarcinoma. Tumour Biol. 33:103–109. 2012. View Article : Google Scholar

19 

Iwahori K, Suzuki H, Kishi Y, et al: Serum HE4 as a diagnostic and prognostic marker for lung cancer. Tumour Biol. 33:1141–1149. 2012. View Article : Google Scholar : PubMed/NCBI

20 

O’Neal RL, Nam KT, LaFleur BJ, et al: Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas. Hum Pathol. 44:734–742. 2013. View Article : Google Scholar

21 

Urban N, Thorpe J, Karlan BY, et al: Interpretation of single and serial measures of HE4 and CA125 in asymptomatic women at high risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev. 21:2087–2094. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Havrilesky LJ, Whitehead CM, Rubatt JM, et al: Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol. 110:374–382. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Anastasi E, Marchei GG, Viggiani V, Gennarini G, Frati L and Reale MG: HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol. 31:113–119. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Schummer M, Drescher C, Forrest R, et al: Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125. Gynecol Oncol. 125:65–69. 2012. View Article : Google Scholar :

25 

Angioli R, Capriglione S, Aloisi A, et al: Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer? Tumour Biol. 35:7009–7015. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Braicu EI, Chekerov R, Richter R, et al: HE4 expression in plasma correlates with surgical outcome and overall survival in patients with first ovarian cancer relapse. Ann Surg Oncol. 21:955–962. 2014. View Article : Google Scholar

27 

Moore RG, Hill EK, Horan T, et al: HE4 (WFDC2) gene over-expression promotes ovarian tumor growth. Sci Rep. 4:35742014. View Article : Google Scholar

28 

Gao L, Cheng HY, Dong L, et al: The role of HE4 in ovarian cancer: inhibiting tumour cell proliferation and metastasis. J Int Med Res. 39:1645–1660. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Kong X, Chang X, Cheng H, Ma R, Ye X and Cui H: Human epididymis protein 4 inhibits proliferation of human ovarian cancer cells via the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT pathways. Int J Gynecol Cancer. 24:427–436. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Xiao Q, Qu K, Wang C, et al: HDGF-related protein-3 is required for anchorage independent survival and chemoresistance in hepatocellular carcinomas. Gut. 62:440–451. 2013. View Article : Google Scholar

31 

Camon E, Magrane M, Barrell D, et al: The Gene Ontology Annotation (GOA) Database: sharing knowledge in Uniprot with Gene Ontology. Nucleic Acids Res. 32:D262–D266. 2004. View Article : Google Scholar :

32 

Zhuang H, Gao J, Hu Z, Liu J, Liu D and Lin B: Co-expression of Lewis y antigen with human epididymis protein 4 in ovarian epithelial carcinoma. PLoS One. 8:e689942013. View Article : Google Scholar : PubMed/NCBI

33 

Lu R, Sun X, Xiao R, Zhou L, Gao X and Guo L: Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. Biochem Biophys Res Commun. 419:274–280. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Hynninen J, Auranen A, Dean K, Lavonius M, Carpen O, Perheentupa A, Seppänen M and Grénman S: Serum HE4 profile during primary chemotherapy of epithelial ovarian cancer. Int J Gynecol Cancer. 21:1573–1578. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang H, Zhu L, Gao J, Hu Z and Lin B: Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells. Oncol Rep 33: 403-412, 2015.
APA
Wang, H., Zhu, L., Gao, J., Hu, Z., & Lin, B. (2015). Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells. Oncology Reports, 33, 403-412. https://doi.org/10.3892/or.2014.3549
MLA
Wang, H., Zhu, L., Gao, J., Hu, Z., Lin, B."Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells". Oncology Reports 33.1 (2015): 403-412.
Chicago
Wang, H., Zhu, L., Gao, J., Hu, Z., Lin, B."Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells". Oncology Reports 33, no. 1 (2015): 403-412. https://doi.org/10.3892/or.2014.3549
Copy and paste a formatted citation
x
Spandidos Publications style
Wang H, Zhu L, Gao J, Hu Z and Lin B: Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells. Oncol Rep 33: 403-412, 2015.
APA
Wang, H., Zhu, L., Gao, J., Hu, Z., & Lin, B. (2015). Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells. Oncology Reports, 33, 403-412. https://doi.org/10.3892/or.2014.3549
MLA
Wang, H., Zhu, L., Gao, J., Hu, Z., Lin, B."Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells". Oncology Reports 33.1 (2015): 403-412.
Chicago
Wang, H., Zhu, L., Gao, J., Hu, Z., Lin, B."Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells". Oncology Reports 33, no. 1 (2015): 403-412. https://doi.org/10.3892/or.2014.3549
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team