Skip to main content

Advertisement

Log in

Decreased CDK10 expression correlates with lymph node metastasis and predicts poor outcome in breast cancer patients - a short report

  • Original Paper
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Background

Cyclin-dependent kinase 10 (CDK10) has recently been identified as a tumor suppressor and, concordantly, its encoding gene has frequently been found to be inactivated in various human cancers. Here, we examined the expression status of CDK10 in a panel of primary human breast cancers and evaluated its correlation with clinicopathological parameters and clinical outcome.

Methods

Western blotting was used to assess CDK10 protein levels in 20 paired breast cancer tissues and adjacent noncancerous tissues. In addition, immunohistochemistry was performed in 128 formalin-fixed, paraffin-embedded tumor tissues. Associations of CDK10 expression with various clinicopathological parameters were evaluated and Kaplan-Meier survival analyses and Cox proportional hazards models were used to estimate its effect on patient survival.

Results

We found that CDK10 protein expression was markedly decreased in cancer tissues compared to adjacent noncancerous tissues. Immunohistochemistry revealed decreased CDK10 levels in 65/128 (50.8 %) of the primary breast cancer tissues tested. These decreased levels were found to be significantly associated with lymph node metastasis (P = 0.003), advanced tumor stage (P < 0.001) and unfavorable overall survival (P < 0.001). Furthermore, multivariate analyses indicated that CDK10 expression may serve as an independent prognostic factor for survival (P = 0.001).

Conclusion

Down-regulated CDK10 expression frequently occurs in breast cancers and correlates with disease progression and poor survival. CDK10 may serve as a prognostic biomarker 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
Fig. 3

Similar content being viewed by others

References

  1. L.A. Torre, F. Bray, R.L. Siegel, J. Ferlay, J. Lortet-Tieulent, A. Jemal, Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87–108 (2015)

    Article  PubMed  Google Scholar 

  2. C.M. Perou, T. Sørlie, M.B. Eisen, M. van de Rijn, S.S. Jeffrey, C.A. Rees, J.R. Pollack, D.T. Ross, H. Johnsen, L.A. Akslen, O. Fluge, A. Pergamenschikov, C. Williams, S.X. Zhu, P.E. Lønning, A.L. Børresen-Dale, P.O. Brown, D. Botstein, Molecular portraits of human breast tumours. Nature 406, 747–752 (2000)

    Article  CAS  PubMed  Google Scholar 

  3. S. Di Cosimo, J. Baselga, Management of breast cancer with targeted agents: importance of heterogeneity. Nat. Rev. Clin. Oncol. 7, 139–147 (2010)

    Article  PubMed  Google Scholar 

  4. J. Peppercorn, C.M. Perou, L.A. Carey, Molecular subtypes in breast cancer evaluation and management: divide and conquer. Cancer Investig. 26, 1–10 (2008)

    Article  CAS  Google Scholar 

  5. S. Tabarestani, S.M. Ghaderian, H. Rezvani, R. Mirfakhraie, A. Ebrahimi, H. Attarian, J. Rafat, M. Ghadyani, H.A. Alavi, N. Kamalian, A. Rakhsha, E. Azargashb, Prognostic and predictive value of copy number alterations in invasive breast cancer as determined by multiplex ligation-dependent probe amplification. Cell. Oncol. 37, 107–118 (2014)

  6. A.H. Verschuur-Maes, C.B. Moelans, P.C. de Bruin, P.J. van Diest, Analysis of gene copy number alterations by multiplex ligation-dependent probe amplification in columnarcell lesions of the breast. Cell. Oncol. 37(147–154) (2014)

  7. E. Yiannakopoulou, Etiology of familial breast cancer with undetected BRCA1 and BRCA2 mutations: clinical implications. Cell. Oncol. 37(1–8) (2014)

  8. L.J. van’t Veer, H. Dai, M.J. van de Vijver, Y.D. He, A.A. Hart, M. Mao, H.L. Peterse, K. van der Kooy, M.J. Marton, A.T. Witteveen, G.J. Schreiber, R.M. Kerkhoven, C. Roberts, P.S. Linsley, R. Bernards, S.H. Friend, Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 530–536 (2002)

    Article  Google Scholar 

  9. Cancer Genome Atlas Network, Comprehensive molecular portraits of human breast tumours. Nature 490, 61–70 (2012)

    Article  Google Scholar 

  10. E.A. Musgrove, R.L. Sutherland, Biological determinants of endocrine resistance in breast cancer. Nat. Rev. Cancer 9, 631–643 (2009)

    Article  CAS  PubMed  Google Scholar 

  11. C.A. Hudis, Trastuzumab-mechanism of action and use in clinical practice. N. Engl. J. Med. 357, 39–51 (2007)

    Article  CAS  PubMed  Google Scholar 

  12. F. Bullrich, T.K. MacLachlan, N. Sang, T. Druck, M.L. Veronese, S.L. Allen, N. Chiorazzi, A. Koff, K. Heubner, C.M. Croce et al., Chromosomal mapping of members of the cdc2 family of protein kinases, cdk3, cdk6, PISSLRE, and PITALRE, and a cdk inhibitor, p27Kip1, to regions involved in human cancer. Cancer Res. 55, 1199–1205 (1995)

    CAS  PubMed  Google Scholar 

  13. J. Crawford, L. Ianzano, M. Savino, S. Whitmore, A.M. Cleton-Jansen, C. Settasatian, M. D’apolito, R. Seshadri, J.C. Pronk, A.D. Auerbach, P.C. Verlander, C.G. Mathew, A.J. Tipping, N.A. Doggett, L. Zelante, D.F. Callen, A. Savoia, The PISSLRE gene: structure, exon skipping, and exclusion as tumor suppressor in breast cancer. Genomics 56, 90–97 (1999)

    Article  CAS  PubMed  Google Scholar 

  14. E. Iorns, N.C. Turner, R. Elliott, N. Syed, O. Garrone, M. Gasco, A.N. Tutt, T. Crook, C.J. Lord, A. Ashworth, Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer. Cancer Cell 13, 91–104 (2008)

    Article  CAS  PubMed  Google Scholar 

  15. C.J. Lord, E. Iorns, A. Ashworth, Dissecting resistance to endocrine therapy in breast cancer. Cell Cycle 7, 1895–1898 (2008)

    Article  CAS  PubMed  Google Scholar 

  16. P. Khanal, H.J. Yun, S.C. Lim, S.G. Ahn, H.E. Yoon, K.W. Kang, R. Hong, H.S. Choi, Proyl isomerase Pin1 facilitates ubiquitin-mediated degradation of cyclin-dependent kinase 10 to induce tamoxifen resistance in breast cancer cells. Oncogene 31, 3845–3856 (2012)

    Article  CAS  PubMed  Google Scholar 

  17. C.W. Yeh, S.H. Kao, Y.C. Cheng, L.S. Hsu, Knockdown of cyclin-dependent kinase 10 (cdk10) gene impairs neural progenitor survival via modulation of raf1a gene expression. J. Biol. Chem. 288, 27927–27939 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. J.H. Yu, X.Y. Zhong, W.G. Zhang, Z.D. Wang, Q. Dong, S. Tai, H. Li, Y.F. Cui, CDK10 functions as a tumor suppressor gene and regulates survivability of biliary tract cancer cells. Oncol. Rep. 27, 1266–1276 (2012)

    PubMed Central  CAS  PubMed  Google Scholar 

  19. X.Y. Zhong, X.X. Xu, J.H. Yu, G.X. Jiang, Y. Yu, S. Tai, Z.D. Wang, Y.F. Cui, Clinical and biological significance of Cdk10 in hepatocellular carcinoma. Gene 498, 68–74 (2012)

    Article  CAS  PubMed  Google Scholar 

  20. Y. You, W. Yang, Z. Wang, H. Zhu, H. Li, C. Lin, Y. Ran, Promoter hypermethylation contributes to the frequent suppression of the CDK10 gene in human nasopharyngeal carcinomas. Cell. Oncol. 36, 323–331 (2013)

    Article  CAS  Google Scholar 

  21. C.Q. Hong, F. Zhang, Y.J. You, W.L. Qiu, A.E. Giuliano, X.J. Cui, G.J. Zhang, Y.K. Cui, Elevated C1orf63 expression is correlated with CDK10 and predicts better outcome for advanced breast cancers: a retrospective study. BMC Cancer 15, 548 (2015)

    Article  PubMed Central  PubMed  Google Scholar 

  22. Y. You, W. Yang, X. Qin, F. Wang, H. Li, C. Lin, W. Li, C. Gu, Y. Zhang, Y. Ran, ECRG4 acts as a tumor suppressor and as a determinant of chemotherapy resistance in human nasopharyngeal carcinoma. Cell. Oncol. 38, 205–14 (2015)

    Article  CAS  Google Scholar 

  23. A.S. Howell, D.J. Lew, Morphogenesis and the cell cycle. Genetics 190(1), 51–77 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. S. Mahale, S.B. Bharate, S. Manda, P. Joshi, P.R. Jenkins, R.A. Vishwakarma, B. Chaudhuri, Antitumour potential of BPT: a dual inhibitor of cdk4 and tubulin polymerization. Cell Death Dis. 6, e1743 (2015)

    Article  CAS  PubMed  Google Scholar 

  25. T. VanArsdale, C. Boshoff, K.T. Arndt, R.T. Abraham, Molecular pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. Clin. Cancer Res. 21, 2905–2910 (2015)

    Article  CAS  PubMed  Google Scholar 

  26. Z. Feng, S. Xu, M. Liu, Y.X. Zeng, T. Kang, Chk1 inhibitor Gö6976 enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy in vitro and in vivo. Cancer Lett. 297, 190–197 (2010)

    Article  CAS  PubMed  Google Scholar 

  27. V.J. Guen, C. Gamble, M. Flajolet, S. Unger, A. Thollet, Y. Ferandin, A. Superti-Furga, P.A. Cohen, L. Meijer, P. Colas, CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome. Proc. Natl. Acad. Sci. U. S. A. 110, 19525–19530 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. G. Heller, B. Ziegler, A. Brandstetter, S. Novak, M. Rudas, G. Hennig, M. Gehrmann, T. Acht, S. Zöchbauer-Müller, M. Filipits, CDK10 is not a target for aberrant DNA methylation in breast cancer. Anticancer Res. 29, 3939–3944 (2009)

    CAS  PubMed  Google Scholar 

  29. A. Dhasarathy, M. Kajita, P.A. Wade, The transcription factor snail mediates epithelial to mesenchymal transitions by repression of estrogen receptor-alpha. Mol. Endocrinol. 21, 2907–2918 (2007)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Y. Ran, S. Wu, Y. You, Demethylation of E-cadherin gene in nasopharyngeal carcinoma could serve as a potential therapeutic strategy. J. Biochem. 149, 49–54 (2011)

Download references

Acknowledgments

This work was supported in part by the Science and Technology Planning Project of Henan Province, China (142102310464), the Key Research Foundation of Higher Education of Henan Province, China (15B320003), the Annual Natural Science Foundation of Luohe Medical College (2015-S-LMC02), the Natural Science Foundation of Hubei Province (2014CFC1154), the Foundation of Medical College of Hubei University of Arts and Science (YXKY 201402) and the Scientific Research Foundation for Doctoral Program of Hubei University of Arts and Science (X. Qin).

Conflicts of interest statement

No potential conflicts of interest were disclosed.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fenglan Gao.

Additional information

Yanjie You and Haijun Li are co-first authors for this manuscript. These authors have 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

You, Y., Li, H., Qin, X. et al. Decreased CDK10 expression correlates with lymph node metastasis and predicts poor outcome in breast cancer patients - a short report. Cell Oncol. 38, 485–491 (2015). https://doi.org/10.1007/s13402-015-0246-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-015-0246-4

Keywords

Navigation