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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
April-2016 Volume 13 Issue 4

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
April-2016 Volume 13 Issue 4

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

Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death

  • Authors:
    • Junqi Wu
    • Linfeng Chi
    • Zhanghui Chen
    • Xianghong Lu
    • Suping Xiao
    • Guanglin Zhang
    • Jindan Luo
    • Ge‑Ming Chen
    • Jun Yang
  • View Affiliations / Copyright

    Affiliations: Clinical Laboratory, Jinhua Hospital of Zhejiang University, Jinhua, Zhejiang 321000, P.R. China, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Pharmacy, Lishui People's Hospital, Lishui, Zhejiang 323000, P.R. China
  • Pages: 3173-3180
    |
    Published online on: February 16, 2016
       https://doi.org/10.3892/mmr.2016.4898
  • 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

The TMPRSS2:E‑twenty‑six (ETS) gene fusion occurs frequently in a high proportion of patients with prostate cancer (PCa) in Western countries, and the aberrant expression of TMPRSS2: v‑ETS avian erythroblastosis virus E26 oncogene homolog (ERG), the most common form of the corresponding protein, can regulate cell migration and contribute to tumor invasion and metastasis. However, its association with other cellular events, and in particular, cell death, remain unknown. To examine the function of such fusion genes, an expression plasmid containing the TMPRSS2:ERG (T1/E5) sequence (ΔERG) from a patient sample was constructed and transiently transfected into DU145 cells, which do not express the fusion gene. It was found that the overexpression of ΔERG significantly inhibited the ability of cisplatin to induce apoptosis in DU145 cells. By contrast, VCaP cells, which do contain TMPRSS2:ERG, were sensitized to cisplatin‑induced apoptosis through siRNA inhibition of the fusion gene. To elucidate the underlying mechanism, a stable cell line expressing the ΔERG gene was constructed. Expression of ΔERG did not affect cell migration, but did protect cells from DNA damage and apoptosis induced by cisplatin. Furthermore, knockdown of ΔERG by short interfering RNA resulted in cells regaining their sensitivity to cisplatin. Finally, the gene coding for activating transcription factor 5, which is important for cell survival, may be upregulated by ΔERG. Taken together, these data point to a new function of the TMPRSS2:ERG fusion gene in regulating the apoptotic pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Siegel R, Naishadham D and Jemal A: Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin. 62:283–298. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, et al: Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 310:644–648. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Falzarano SM and Magi-Galluzzi C: ERG protein expression as a biomarker of prostate cancer. Biomark Med. 7:851–865. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Helgeson BE, Tomlins SA, Shah N, Laxman B, Cao Q, Prensner JR, Cao X, Singla N, Montie JE, Varambally S, et al: Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer. Cancer Res. 68:73–80. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Tomlins SA, Laxman B, Varambally S, Cao X, Yu J, Helgeson BE, Cao Q, Prensner JR, Rubin MA, Shah RB, et al: Role of the TMPRSS2-ERG gene fusion in prostate cancer. Neoplasia. 10:177–188. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Klezovitch O, Risk M, Coleman I, Lucas JM, Null M, True LD, Nelson PS and Vasioukhin V: A causal role for ERG in neoplastic transformation of prostate epithelium. Proc Natl Acad Sci USA. 105:2105–2110. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Tian TV, Tomavo N, Huot L, Flourens A, Bonnelye E, Flajollet S, Hot D, Leroy X, de Launoit Y and Duterque-Coquillaud M: Identification of novel TMPRSS2:ERG mechanisms in prostate cancer metastasis: Involvement of MMP9 and PLXNA2. Oncogene. 33:2204–2214. 2014. View Article : Google Scholar

8 

Shao L, Zhou Z, Cai Y, Castro P, Dakhov O, Shi P, Bai Y, Ji H, Shen W and Wang J: Celastrol suppresses tumor cell growth through targeting an AR-ERG-NF-kB pathway in TMPRSS2/ERG fusion gene expressing prostate cancer. PLoS One. 8:e583912013. View Article : Google Scholar

9 

Loehrer PJ and Einhorn LH: Drugs five years later. Cisplatin Ann Intern Med. 100:704–713. 1984. View Article : Google Scholar

10 

Prestayko AW, D'Aoust JC, Issell BF and Crooke ST: Cisplatin (cis-diamminedichloroplatinum II). Cancer Treat Rev. 6:17–39. 1979. View Article : Google Scholar : PubMed/NCBI

11 

Eastman A: The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacol Ther. 34:155–166. 1987. View Article : Google Scholar : PubMed/NCBI

12 

Oh WK, Tay MH and Huang J: Is there a role for platinum chemotherapy in the treatment of patients with hormone-refractory prostate cancer? Cancer. 109:477–486. 2007. View Article : Google Scholar

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

14 

Carver BS, Tran J, Gopalan A, Chen Z, Shaikh S, Carracedo A, Alimonti A, Nardella C, Varmeh S, Scardino PT, et al: Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate. Nat Genet. 41:619–624. 2009. View Article : Google Scholar : PubMed/NCBI

15 

King JC, Xu J, Wongvipat J, Hieronymus H, Carver BS, Leung DH, Taylor BS, Sander C, Cardiff RD, Couto SS, et al: Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis. Nat Genet. 41:524–526. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Esgueva R, Perner S, J LaFargue C, Scheble V, Stephan C, Lein M, Fritzsche FR, Dietel M, Kristiansen G and Rubin MA: Prevalence of TMPRSS2-ERG and SLC45A3-ERG gene fusions in a large prostatectomy cohort. Mod Pathol. 23:539–546. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Galluzzi L, Aaronson SA, Abrams J, Alnemri ES, Andrews DW, Baehrecke EH, Bazan NG, Blagosklonny MV, Blomgren K, Borner C, et al: Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes. Cell Death Differ. 16:1093–1107. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, et al: Molecular definitions of cell death subroutines: Recommendations of the nomenclature committee on cell death 2012. Cell Death Differ. 19:107–120. 2012. View Article : Google Scholar :

19 

Hai TW, Liu F, Coukos WJ and Green MR: Transcription factor ATF cDNA clones: An extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 3:2083–2090. 1989. View Article : Google Scholar : PubMed/NCBI

20 

Papandreou CN, Daliani DD, Thall PF, Tu SM, Wang X, Reyes A, Troncoso P and Logothetis CJ: Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully char-acterized small-cell carcinoma of the prostate. J Clin Oncol. 20:3072–3080. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Berry W, Friedland D, Fleagle J, Jackson D, Ilegbodu D, Boehm KA and Asmar L: A phase II study of weekly paclitaxel/estramustine/carboplatin in hormone-refractory prostate cancer. Clin Genitourin Cancer. 5:131–137. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ and Green DR: The BCL-2 family reunion. Mol Cell. 37:299–310. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Harris MH and Thompson CB: The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ. 7:1182–1191. 2000. View Article : Google Scholar

24 

Persengiev SP and Green MR: The role of ATF/CREB family members in cell growth, survival and apoptosis. Apoptosis. 8:225–228. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Persengiev SP, Devireddy LR and Green MR: Inhibition of apoptosis by ATFx: A novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors. Genes Dev. 16:1806–1814. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Zhou C, Li Z, Diao H, Yu Y, Zhu W, Dai Y, Chen FF and Yang J: DNA damage evaluated by gammaH2AX foci formation by a selective group of chemical/physical stressors. Mutat Res. 604:8–18. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Brenner JC, Ateeq B, Li Y, Yocum AK, Cao Q, Asangani IA, Patel S, Wang X, Liang H, Yu J, et al: Mechanistic rationale for inhibition of poly (ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell. 19:664–678. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Han S, Brenner JC, Sabolch A, Jackson W, Speers C, Wilder-Romans K, Knudsen KE, Lawrence TS, Chinnaiyan AM and Feng FY: Targeted radiosensitization of ETS fusion-positive prostate cancer through PARP1 inhibition. Neoplasia. 15:1207–1217. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Haffner MC, Aryee MJ, Toubaji A, Esopi DM, Albadine R, Gurel B, Isaacs WB, Bova GS, Liu W, Xu J, et al: Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. Nat Genet. 42:668–675. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wu J, Chi L, Chen Z, Lu X, Xiao S, Zhang G, Luo J, Chen GM and Yang J: Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death. Mol Med Rep 13: 3173-3180, 2016.
APA
Wu, J., Chi, L., Chen, Z., Lu, X., Xiao, S., Zhang, G. ... Yang, J. (2016). Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death. Molecular Medicine Reports, 13, 3173-3180. https://doi.org/10.3892/mmr.2016.4898
MLA
Wu, J., Chi, L., Chen, Z., Lu, X., Xiao, S., Zhang, G., Luo, J., Chen, G., Yang, J."Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death". Molecular Medicine Reports 13.4 (2016): 3173-3180.
Chicago
Wu, J., Chi, L., Chen, Z., Lu, X., Xiao, S., Zhang, G., Luo, J., Chen, G., Yang, J."Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death". Molecular Medicine Reports 13, no. 4 (2016): 3173-3180. https://doi.org/10.3892/mmr.2016.4898
Copy and paste a formatted citation
x
Spandidos Publications style
Wu J, Chi L, Chen Z, Lu X, Xiao S, Zhang G, Luo J, Chen GM and Yang J: Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death. Mol Med Rep 13: 3173-3180, 2016.
APA
Wu, J., Chi, L., Chen, Z., Lu, X., Xiao, S., Zhang, G. ... Yang, J. (2016). Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death. Molecular Medicine Reports, 13, 3173-3180. https://doi.org/10.3892/mmr.2016.4898
MLA
Wu, J., Chi, L., Chen, Z., Lu, X., Xiao, S., Zhang, G., Luo, J., Chen, G., Yang, J."Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death". Molecular Medicine Reports 13.4 (2016): 3173-3180.
Chicago
Wu, J., Chi, L., Chen, Z., Lu, X., Xiao, S., Zhang, G., Luo, J., Chen, G., Yang, J."Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death". Molecular Medicine Reports 13, no. 4 (2016): 3173-3180. https://doi.org/10.3892/mmr.2016.4898
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