Skip to main content

Advertisement

SpringerLink
Log in

The General Expression Analysis of WTX Gene in Normal and Cancer Tissues

  • Short Communication
  • Published:
Pathology & Oncology Research

Abstract

WTX (Wilms’ tumor suppressor X chromosome) is a novel putative tumor suppressor gene in Wilms’ tumor of kidney, its expression and function in other human cancers had not been explored. This study detected the expression of WTX in 459 cases of 15 organs of cancers and adjacent normal tissues by using immunohistochemical staining (IHC), and validated them by in situ hybridization (ISH) and quantitative real-time reverse transcription PCR (qRT-PCR). IHC and ISH data showed that WTX protein was generally expressed in normal tissues, but reduced expression in corresponding cancers. This study demonstrated that WTX downregulation is a common phenomenon in human cancers, WTX might be a general tumor-suppressor gene and biological marker of multiple cancer tissues. Apart from kidney, stomach is another target tissue of WTX gene. The germline and somatic mutations of WTX were screened in 12 gastric cancer patients and identified in one cases (8.3%). Mutation in the WTX gene might be one of the reasons of WTX loss in gastric cancer patients.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Rivera MN, Kim WJ, Wells J, Driscoll DR, Brannigan BW, Han M, Kim JC, Feinberg AP, Gerald WL, Vargas SO, Chin L, Iafrate AJ, Bell DW, Haber DA (2007) An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science 315(5812):642–645

    Article  CAS  PubMed  Google Scholar 

  2. Alexandrescu, S., S. Akhavanfard, M.H. Harris, and S.O. Vargas, Clinical, pathologic, and genetic features of Wilms tumors with WTX gene mutation. Pediatr Dev Pathol, 2016.

  3. X-ing Out Tumor Suppression. Science, 2007. 315: p. 569 h.

  4. Bagchi S (2007) New tumour suppressor linked to Wilms’ tumour. Lancet Oncol 8(2):102

    Article  PubMed  Google Scholar 

  5. Kim MK, Min DJ, Rabin M, Licht JD (2011) Functional characterization of Wilms tumor-suppressor WTX and tumor-associated mutants. Oncogene 30(7):832–842

    Article  CAS  PubMed  Google Scholar 

  6. Jenkins ZA, van Kogelenberg M, Morgan T, Jeffs A, Fukuzawa R, Pearl E, Thaller C, Hing AV, Porteous ME, Garcia-Minaur S, Bohring A, Lacombe D, Stewart F, Fiskerstrand T, Bindoff L, Berland S, Ades LC, Tchan M, David A, Wilson LC, Hennekam RC, Donnai D, Mansour S, Cormier-Daire V, Robertson SP (2009) Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. Nat Genet 41(1):95–100

    Article  CAS  PubMed  Google Scholar 

  7. Fujita A, Ochi N, Fujimaki H, Muramatsu H, Takahashi Y, Natsume J, Kojima S, Nakashima M, Tsurusaki Y, Saitsu H, Matsumoto N, Miyake N (2014) A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma. Am J Med Genet A 164A(4):998–1002

    Article  PubMed  Google Scholar 

  8. Comai G, Boutet A, Neirijnck Y, Schedl A (2010) Expression patterns of the Wtx/Amer gene family during mouse embryonic development. Dev Dyn 239(6):1867–1878

    Article  CAS  PubMed  Google Scholar 

  9. He L, Ding Y, Zhang Q, Che X, He Y, Shen H, Wang H, Li Z, Zhao L, Geng J, Deng Y, Yang L, Li J, Cai J, Qiu L, Wen K, Xu X, Jiang S (2006) Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol 210(3):288–297

    Article  CAS  PubMed  Google Scholar 

  10. Qingling Z, Lina Y, Li L, Shuang W, Yufang Y, Yi D, Divakaran J, Xin L, Yanqing D (2011) LMP1 antagonizes WNT/beta-catenin signalling through inhibition of WTX and promotes nasopharyngeal dysplasia but not tumourigenesis in LMP1(B95-8) transgenic mice. J Pathol 223(5):574–583

    Article  PubMed  Google Scholar 

  11. Major MB, Camp ND, Berndt JD, Yi X, Goldenberg SJ, Hubbert C, Biechele TL, Gingras AC, Zheng N, Maccoss MJ, Angers S, Moon RT (2007) Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science 316(5827):1043–1046

    Article  CAS  PubMed  Google Scholar 

  12. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  13. Armat M, Ramezani F, Molavi O, Sabzichi M, Samadi N (2016) Six family of homeobox genes and related mechanisms in tumorigenesis protocols. Tumori:0

  14. Kress E, Skah S, Sirakov M, Nadjar J, Gadot N, Scoazec JY, Samarut J, Plateroti M (2010) Cooperation between the thyroid hormone receptor TRalpha1 and the WNT pathway in the induction of intestinal tumorigenesis. Gastroenterology 138(5):1863–1874

    Article  CAS  PubMed  Google Scholar 

  15. Rivlin N, Brosh R, Oren M, Rotter V (2011) Mutations in the p53 tumor suppressor Gene: important milestones at the various steps of tumorigenesis. Genes Cancer 2(4):466–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Holloway KR, Sinha VC, Bu W, Toneff M, Dong J, Peng Y, Li Y (2016) Targeting oncogenes into a defined subset of mammary cells demonstrates that the initiating oncogenic mutation defines the resulting tumor phenotype. Int J Biol Sci 12(4):381–388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhou QM, Li W, Zhang X, Chen YB, Chen XC, Guan YX, Ding Y, Wen XZ, Xia Q, Zhou Q, Peng RQ, Hou JH, Zhu XF, Zeng YX, Zhang XS (2012) The mutation profiles of common oncogenes involved in melanoma in southern China. J Invest Dermatol 132(7):1935–1937

    Article  CAS  PubMed  Google Scholar 

  18. Evangelisti C, de Biase D, Kurelac I, Ceccarelli C, Prokisch H, Meitinger T, Caria P, Vanni R, Romeo G, Tallini G, Gasparre G, Bonora E (2015) A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors. BMC Cancer 15:157

    Article  PubMed  PubMed Central  Google Scholar 

  19. Perotti D, Gamba B, Sardella M, Spreafico F, Terenziani M, Collini P, Pession A, Nantron M, Fossati-Bellani F, Radice P (2008) Functional inactivation of the WTX gene is not a frequent event in Wilms’ tumors. Oncogene 27(33):4625–4632

    Article  CAS  PubMed  Google Scholar 

  20. Fukuzawa R, Holman SK, Chow CW, Savarirayan R, Reeve AE, Robertson SP (2010) WTX mutations can occur both early and late in the pathogenesis of Wilms tumour. J Med Genet 47(11):791–794

    Article  CAS  PubMed  Google Scholar 

  21. Scheel SK, Porzner M, Pfeiffer S, Ormanns S, Kirchner T, Jung A (2010) Mutations in the WTX-gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers. BMC Cancer 10:413

    Article  PubMed  PubMed Central  Google Scholar 

  22. Chung NG, Kim MS, Chung YJ, Yoo NJ, Lee SH (2008) Tumor suppressor WTX gene mutation is rare in acute leukemias. Leuk Lymphoma 49(8):1616–1617

    Article  PubMed  Google Scholar 

  23. Zilberman D, Coleman-Derr D, Ballinger T, Henikoff S (2008) Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 456(7218):125–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Liu X, Wang Q, Niu H, Yang X, Sun J, Zhang Q, Ding Y (2013) Promoter methylation of Wilms’ tumor gene on the X- chromosome in gastric cancer. Nan Fang Yi Ke Da Xue Xue Bao 33(3):318–321

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work was supported by the National Natural Science Foundation of China (QLZ, 81472712, 81272760, 81071989); Science and Technology Project of Guangdong Province, China (QLZ, 2012B060300019); Guangdong Provincial Natural Science Foundation of China (QLZ, S2011010004178).

Author information

Authors and Affiliations

  1. Department of Pathology, Nanfang Hospital, Guangzhou, 510515, People’s Republic of China

    Yao-Yao Zhang, Qi-Ming Wang, Hui-Lin Niu, Xia Liu & Qing-Ling Zhang

  2. Department of Pathology, College of Basic Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Yao-Yao Zhang, Qi-Ming Wang, Hui-Lin Niu, Xia Liu & Qing-Ling Zhang

Authors
  1. Yao-Yao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qi-Ming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hui-Lin Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xia Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing-Ling Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing-Ling Zhang.

Additional information

Yao-Yao Zhang and Qi-Ming Wang Contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, YY., Wang, QM., Niu, HL. et al. The General Expression Analysis of WTX Gene in Normal and Cancer Tissues. Pathol. Oncol. Res. 23, 439–446 (2017). https://doi.org/10.1007/s12253-016-0168-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-016-0168-0

Keywords

Search

Navigation