Skip to main content

Advertisement

Log in

Thymopoietin Beta and Gamma Isoforms as a Potential Diagnostic Molecular Marker for Breast Cancer: Preliminary Data

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Thymopoietin (TMPO) is an inner nuclear membrane protein, the coding gene named equally, can give arise to six isoforms by alternative splicing. This gene has been found up regulated in several types of cancer. At present work, we evaluated the TMPO isoforms generated by alternative splicing as well as the protein signal detection in breast cancer samples. TMPO expression was analyzed by immunohistochemistry in tissue microarray containing 46 breast tissue samples including normal (n = 6), benign lesions (n = 18) (fibroadenomas (n = 6), fibrocystic changes (n = 6), ductal hyperplasias (n = 6)) and breast carcinoma (n = 22). Isoforms -α, −β and -γ of TMPO were evaluated using RT-PCR; clinical-pathological correlation analysis were done by mean of X2. Neither the normal nor the benign lesions of the breast showed positive TMPO immunodetection, whilst 45 % of the breast carcinomas were immunopositive (p = 0.000), nine of ten positives carcinomas correspond to the Luminal A subtype. Further, alpha isoform was present in all breast samples analyzed; however, beta and gamma isoforms were only present in ten (p = 0.003) and 17 (p = 0.000), respectively, in the breast cancer samples. According with the present data, we suggest that TMPOβ and -γ isoforms could provide a potential reliable diagnostic marker for breast cancer.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Knaul FM, Nigenda B, Lozano R, Arreola H, Langer A, Frenk J (2008) Breast cancer in Mexico: a pressing priority. Reprod Health Matters 16:113–123

    Article  PubMed  Google Scholar 

  2. Cantile M, Pettinato G, Procino A, Feliciello I, Cindolo L, Cillo C (2003) In vivo expression of the whole HOX gene network in human breast cancer. Eur J Cancer 39:257–264

    Article  CAS  PubMed  Google Scholar 

  3. Harris C, Andryuk P, Cline S, Mathew S, Siekerka J, Goldstein G (1995) Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO B to rat lamin-associated polypeptide 2. Genomics 28:198

    Article  CAS  PubMed  Google Scholar 

  4. Ward M, van der Watt P, Tzoneva G, Leaner V (2011) Deregulated LAP2a expression in cervical cancer associates with aberrant E2F and p53 activities. IUBMB Life 11:1018–1026

    Article  Google Scholar 

  5. Parise P, Finocchiaro G, Masciadri B, Quarto M, Francois S, Mancuso F et al (2006) Lap2α expression is controlled by E2F and deregulated in various human tumors. Cell Cycle 12:1331–1341

    Article  Google Scholar 

  6. LaTulippe E, Satagopan J, Smith A, Scher H, Scardino P, Reuter V et al (2002) Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res 62:4499–506

    CAS  PubMed  Google Scholar 

  7. Agrawal D, Chen T, Irby R, Quackenbush J, Chambers A, Szabo M et al (2002) Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst 94:513–521

    Article  CAS  PubMed  Google Scholar 

  8. Marrero D, Peralta R, Valdivia A, De la Mora A, Romero P, Parra M et al (2012) The neurofibromin 1 type I isoform predominance characterises female population affected by sporadic breast cancer: preliminary data. J Clin Pathol 5:419–423

    Article  Google Scholar 

  9. Hugh J, Hanson J, Chon U, Nielsen T, Perou C, Dumontet C et al (2009) Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol 8:1168–1176

    Article  Google Scholar 

  10. Dorner D, Vlcek S, Foeger N, Gajewski A, Makolm C, Gotzmann J et al (2006) Lamina-associated polypeptide 2α regulates cell cycle progression and differentiation via the retinoblastoma–E2F pathway. J Cell Biol 1:83–93

    Article  Google Scholar 

  11. Kim H, Hwang H, Han M, Baek S, Sim H, Yoon S et al (2012) LAP2 Is widely overexpressed in diverse digestive tract cancers and regulates motility of cancer cells. Plos One 6:e39482

    Article  Google Scholar 

  12. Taylor MR, Slavov D, Gajewski A, Vlcek S, Ku L, Fain PR et al (2005) Thymopoietin (Lamina-Associated Polypeptide 2) gene mutation associated with dilated cardiomyopathy. Hum Mutat 6:566–574

    Article  Google Scholar 

  13. Dechat T, Gotzmann J, Stockinger A, Harris C, Talle M, Siekierka J et al (1998) Detergent-salt resistance of LAP2α in interphase nuclei and phosphorylation-dependent association with chromosomes early in nuclear assembly implies functions in nuclear structure dinamics. EMBO J 17:4887–4902

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. McCafferty M, Healy N, Kerin M (2009) Breast cancer subtypes and molecular biomarkers. Diagn Histopathol 15:485–489

    Article  Google Scholar 

  15. Staples E, Gasiewicz T, Fiore N, Lubahn D, Korach K, Silverstone A (1999) Estrogen receptor is necessary in thymic development and estradiol-induced thymic alterations. J Anat 163:4168–4174

    CAS  Google Scholar 

  16. Ertel A, Dean J, Rui H, Liu C, Witkiewicz A, Knudsen KE et al (2010) RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeuti responsse. Cell Cycle 20:4153–4163

    Article  Google Scholar 

  17. Zhang S, Liu S, Al-Saleem L, Holloran D, Babb J, Guo X et al (2000) E2F-1: a proliferative marker of breast neoplasia. Cancer Epidemiol Biomarkers Prev 9:395–401

  18. Moroy T, Heyd F (2007) The impact of alternative splicing in vivo: mouse models show the way. RNA 13:1155–1171

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Venables J, Klinck R, Bramard A, Inkel L, Dufresne-Martin G, Koh C et al (2008) Identification of alternative splicing markers for breast cancer. Cancer Res 22:9525–9531

    Article  Google Scholar 

  20. Vlcek S, Korbei B, Foisner R (2002) Distinct functions of the unique C terminus of LAP2 in cell proliferation and nuclear assembly. J Biol Chem 21:18898–18907

    Article  Google Scholar 

  21. Martins S, Eikvar S, Furukawa K, Collas P (2003) HA95 and LAP2 mediate a novel chromatin–nuclear envelope interaction implicated in initiation of DNA replication. J Cell Biol 2:177–188

    Article  Google Scholar 

  22. Gant T, Harris C, Wilson K (1999) Roles of LAP2 proteins in nuclear assembly and DNA replication: truncated LAP2b proteins alter lamina assembly, envelope formation, nuclear size, and DNA replication efficiency in Xenopus laevis extracts. J Cell Biol 6:1083–1096

    Article  Google Scholar 

  23. Dechat T, Vlcek S, Foisner R (2000) Review: lamina-associated polypeptide 2 isoforms and related proteins in cell cycle-dependent nuclear structure dynamics. J Struct Biol 129:335–345

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was partially supported by a grant FIS-IMSS (Mexico). During this work DMR, KTP, PRM, MMR, LPG and MRE were recipients of a CONACyT fellowship.

Competing Interests

The authors declare that there is not conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mauricio Salcedo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marrero-Rodríguez, D., Taniguchi-Ponciano, K., Lopez-Sleman, J. et al. Thymopoietin Beta and Gamma Isoforms as a Potential Diagnostic Molecular Marker for Breast Cancer: Preliminary Data. Pathol. Oncol. Res. 21, 1045–1050 (2015). https://doi.org/10.1007/s12253-015-9907-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-015-9907-x

Keywords

Navigation