Skip to main content
SpringerLink
Log in

Expression and significance of SHP-2 in human papillomavirus infected cervical cancer

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

This study investigated the expression and prognostic value of SHP-2 in cervical cancer caused by human papillomavirus (HPV) infection. Forty-five specimens from patients with cervical cancer (stage I–III), 32 specimens from patients with cervical intraepithelial neoplasia (CIN) (I, II) and 20 normal cervical samples from patients with hysteromyoma were collected in Department of Pathology for comparison. The expression levels of SHP-2 and IFN-β proteins were detected by using immunohistochemistry. The mRNA expression level of SHP-2 was detected by using quantitative real-time polymerase chain reaction (PCR). HPVs were detected by HPV GenoArray Test. The Spearman correlation was used to compare the expression level of SHP-2 in HPV infected cervical cancer vs non-HPV infected normal cervix. The level of SHP-2 protein expression in the cancer tissues (88.8%) was significantly higher than in CIN tissues (62.5%) and normal cervixes (45%) (P<0.05 and P<0.05, respectively). The SHP-2 mRNA levels in the cancer tissues were upregulated as compared with those in the normal cervixes (P<0.05). Twenty-one (46.7%) cervical cancers, 25 (78.1%) CINs and 17 (85%) normal cervixes showed IFN-β positive staining in cytoplasm. There was statistically significant difference in the expression rate of IFN-β between cervical cancer and normal cervix (χ 2=8.378, P<0.05) as well as between cervical cancer and CIN (χ 2=7.695, P<0.05). HPV16/18 infections could be found in normal cervixs (15%), CINs (68.7%) and cervical cancers (84.4%). There was a correlation between HPV infection and SHP-2 expression in cervical cancer (r s=0.653, P<0.05). SHP-2 may be a useful prognostic and diagnostic indicator for HPV infected cervical cancer. In cervical cancers, SHP-2 mRNA and protein overexpression was associated with IFN-β lower-expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Matthews RJ, Bowne DB, Flores E, et al. Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences. Mol Cell Biol, 1992,12(5):2396–2405

    PubMed  CAS  Google Scholar 

  2. Neel BG, Gu H, Pao L. The ’shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem, 2003,28(6):284–293

    Article  CAS  Google Scholar 

  3. Kharitonenkov A, Chen Z, Sures I, et al. A family of proteins that inhibit signaling through tyrosine kinase receptors. Nature, 1997,386(6621):181–186

    Article  PubMed  CAS  Google Scholar 

  4. Bennett AM, Tang TL, Sugimoto S, et al. Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras. Proc Natl Acad, 1994,91(15):7335–7339

    Article  CAS  Google Scholar 

  5. Qu CK. The SHP-2 tyrosine phosphatase: Signaling mechanisms and biological functions. Cell Res, 2000, 10(4):279–288

    Article  PubMed  CAS  Google Scholar 

  6. You M, Flick LM, Yu D, et al. Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor. J Exp Med, 2001,193(1):101–110

    Article  PubMed  CAS  Google Scholar 

  7. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 1999,189(1):12–19

    Article  PubMed  CAS  Google Scholar 

  8. Bryan JT. Developing an HPV vaccine to prevent cervical cancer and genital warts. Vaccine, 2007,25(16):3001–3006

    Article  PubMed  CAS  Google Scholar 

  9. Lee KM, Chuang E, Griffin M, et al. Molecular basis of T cell inactivation by CTLA-4. Science, 1998,282(5397): 2263–2266

    Article  PubMed  CAS  Google Scholar 

  10. Yu WM, Hawley TS, Hawley RG, et al. Catalytic-dependent and independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling. Oncogene, 2003,22(38):5995–6004

    Article  PubMed  CAS  Google Scholar 

  11. Huang Q, Lerner-Marmarosh N, Che W, et al. The novel role of the C-terminal region of SHP-2 involvement of Gab1 and SHP-2 phosphatase activity in Elk-1 activation. J Biol Chem, 2002,277(32):29 330–29 341

    CAS  Google Scholar 

  12. Ahmad S, Banville D, Zhao Z, et al. A widely expressed human protein-tyrosine phosphatase containing src homology 2 domains. Proc Natl Acad, 1993,90(6):2197–2201

    Article  CAS  Google Scholar 

  13. Feng GS, Hui CC, Pawson T. SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine kinases. Science, 1993,259(5101):1607–1611

    Article  PubMed  CAS  Google Scholar 

  14. Vogel W, Lammers R, Huang J, et al. Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science, 1993,259(5101):1611–1614

    Article  PubMed  CAS  Google Scholar 

  15. Ke Y, Zhang EE, Hagihara K, et al. Deletion of Shp2 in the brain leads to defective proliferation and differentiation in neural stem cells and early postnatal lethality. Mol Cell Biol, 2007,27(19):6706–6717

    Article  PubMed  CAS  Google Scholar 

  16. Voena C, Conte C, Ambrogio C, et al. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. Cancer Res, 2007,67(9):4278–4286

    Article  PubMed  CAS  Google Scholar 

  17. Xu R. Shp-2, a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia. Cell Res, 2007,17(4):295–297

    Article  PubMed  CAS  Google Scholar 

  18. Hao XP, Pretlow TG, Rao JS, et al. Beta-catenin expression is altered in human colonic aberrant crypt foci. Cancer Res, 2001,61(22):8085–8088

    PubMed  CAS  Google Scholar 

  19. Jarboe JS, Johnson KR, Choi Y, et al. Expression of interleukin-13 receptor α2 in glioblastoma multiforme: implications for targeted therapies. Cancer Res, 2007,67(17): 7983–7986

    Article  PubMed  CAS  Google Scholar 

  20. An HZ, Zhao W, Hou J, et al. SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production. Immunity, 2006,25(6):919–928

    Article  PubMed  CAS  Google Scholar 

  21. Fitzgerald KA, McWhirter SM, Faia KL, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol, 2003,4(5):491–496

    Article  PubMed  CAS  Google Scholar 

  22. Wang Y, Chen T, Han C. Lysosome-associated small Rab GTPase Rab7b negatively regulates TLR4 signaling in macrophages by promoting lysosomal degradation of TLR4. Blood, 2007,110(3):962–971

    Article  PubMed  CAS  Google Scholar 

  23. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol, 2003,21(1):335–376

    Article  PubMed  CAS  Google Scholar 

  24. You M, Flick LM, Yu D, et al. Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor. J Exp Med, 2001,193(1):101–110

    Article  PubMed  CAS  Google Scholar 

  25. Du Z, Shen Y, Yang W, et al. Inhibition of IFN-a signaling by a PKC- and protein tyrosine phosphatase SHP-2-dependent pathway. Proc Natl Acad, 2005, 102(29):10 267–10 272

    Article  CAS  Google Scholar 

  26. You M, Yu DH, Feng GS. Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated JAK/STAT pathway. Mol Cell Biol, 1999,19(3):2416–2424

    PubMed  CAS  Google Scholar 

  27. Hong F, Nguyen VA, Gao B. Tumor necrosis factor α attenuates interferon α signaling in the liver: involvement of SOCS3 and SHP2 and implication in resistance to interferon therapy. FASEB J, 2001,15(9):1595–1597

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, China

    Fei Meng  (孟 斐) & Shulan Zhang  (张淑兰)

  2. Department of Microbiology and Cell Biology, Shenyang Pharmaceutical University School of Life Science and Biopharmaceutics, Shenyang, 110016, China

    Xiaoyun Zhao  (赵晓云)

Authors
  1. Fei Meng  (孟 斐)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoyun Zhao  (赵晓云)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shulan Zhang  (张淑兰)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shulan Zhang  (张淑兰).

Additional information

This project was supported by a grant from the National Natural Science Foundation of China (No. 30973191).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meng, F., Zhao, X. & Zhang, S. Expression and significance of SHP-2 in human papillomavirus infected cervical cancer. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 32, 247–251 (2012). https://doi.org/10.1007/s11596-012-0044-4

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-012-0044-4

Key words

Search

Navigation