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Expression of Ki-67, Bcl-2, Survivin and p53 Proteins in Patients with Pulmonary Carcinoma

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Respiratory Regulation - The Molecular Approach

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 756))

Abstract

Apoptosis is the fundamental process necessary for eliminating damaged or mutated cells. Alterations in the apoptotic pathway appear to be key events in cancer development and progression. Bcl-2 is the key member of the Bcl-2 family of apoptosis regulator proteins with anti-apoptotic effects. Survivin acts as an inhibitor of apoptosis as well and has been implicated in both inhibition of apoptosis and mitosis regulation. p53 is one of the tumor suppressor proteins, prevents tumor formation through cell cycle blocking and eliminates damaged cells via the activation of apoptosis. The Ki-67 protein is a cellular marker for proliferation. To investigate the possible interactions of the aforementioned proteins, we examined their expression in 76 patients with diagnosed lung cancer using immunohistochemical visualisation. Ki-67 protein was expressed in the cancer cells of all patients with small cell lung cancer (SCLC). We found a negative correlation between survivin and p53 expression. A decreased intensity of survivin expression and fewer cells positive for survivin (66.7%) in SCLC in comparison with other lung cancer types (98.0%) was detected. Reversely, expression of Bcl-2 was found in more than 90% of cases with SCLC. We hypothesize that high expression and intensity of Bcl-2 protein could be a factor behind a bad prognosis in SCLC.

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References

  • Akyürek, N., Memiş, L., Ekinci, O., Köktürk, N., & Oztürk, C. (2006). Survivin expression in pre-invasive lesions and non-small cell lung carcinoma. Virchows Archiv, 449(2), 164–170.

    Article  PubMed  Google Scholar 

  • Altieri, D. C. (2003). Validating survivin as a cancer therapeutic target. Nature Reviews. Cancer, 3, 46–54.

    Article  PubMed  CAS  Google Scholar 

  • Borner, Ch. (1996). Diminished cell proliferation associated with the deathprotective activity of Bcl-2. Journal of Biological Chemistry, 271(22), 12695–12698.

    PubMed  CAS  Google Scholar 

  • Coutts, A. S., & Thangue, N. (2006). The p53 response during DNA damage: Impact of transcriptional cofactors. Biochemical Society Symposium, 73, 181–189.

    PubMed  CAS  Google Scholar 

  • Deng, Y., & Wu, X. (2000). Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria. Proceedings of the National Academy of Sciences of the USA, 97, 12050–12055.

    Article  PubMed  CAS  Google Scholar 

  • Fan, J., Wang, L., Jiang, G. N., He, W. X., & Ding, J. A. (2008). The role of survivin on overall survival of non-small cell lung cancer, a meta-analysis of published literatures. Lung Cancer, 61, 91–96.

    Article  PubMed  Google Scholar 

  • Ferlay, J., Parkin, D. M., & Steliarova-Foucher, E. (2010). Estimates of cancer incidence and mortality in Europe in 2008. European Journal of Cancer, 46(4), 765–781.

    Article  PubMed  CAS  Google Scholar 

  • Han, B., Lin, S., Yu, L. J., Wang, R. Z., & Wang, Y. Y. (2009). Correlation of 18F-FDG PET activity with expressions of survivin, Ki-67, and CD34 in non-small-cell lung cancer. Nuclear Medicine Communications, 30(11), 831–837.

    Article  PubMed  CAS  Google Scholar 

  • Higashiyama, M., Doi, O., Kodama, K., Yokouchi, H., & Tateishi, R. (1995). High prevalence of Bcl-2 oncoprotein expression in small cell lung cancer. Anticancer Research, 15(2), 503–505.

    PubMed  CAS  Google Scholar 

  • Isobe, M., Emanuel, B. S., Givol, D., Oren, M., & Croce, C. M. (1986). Localization of gene for human p53 tumor antigen to band 17p13. Nature, 320(6057), 84–85.

    Article  PubMed  CAS  Google Scholar 

  • Jiang, S. X., Sato, Y., Kuwao, S., & Kameya, T. (1995). Expression of Bcl-2 oncogene protein is prevalent in small cell lung carcinomas. The Journal of Pathology, 177(2), 135–138.

    Article  PubMed  CAS  Google Scholar 

  • Jin, H. O., Yoon, S. I., Seo, S. K., Lee, H. C., Woo, S. H., Yoo, D. H., Lee, S. J., Choe, T. B., An, S., Kwon, T. J., Kim, J. I., Park, M. J., Hong, S. I., Park, I. C., & Rhee, C. H. (2006). Synergistic induction of apoptosis by sulindac and arsenic trioxide in human lung cancer A549 cells via reactive oxygen species-dependent down-regulation of survivin. Biochemical Pharmacology, 72(10), 1228–1236.

    Article  PubMed  CAS  Google Scholar 

  • Jinz, Z., & El-Deiry, W. S. (2005). Overview of cell death signaling pathways. Cancer Biology & Therapy, 4, 139–163.

    Article  Google Scholar 

  • Kawasaki, H., Altieri, D. C., Lu, C. D., Toyoda, M., Tenjo, T., & Tanigawa, N. (1998). Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Research, 58, 179–185.

    Google Scholar 

  • Kitada, S., Takayama, S., De Riel, K., Tanaka, S., & Reed, J. C. (1994). Reversal of chemoresistance of lymphoma cells by antisense-mediated reduction of Bcl-2 gene expression. Antisense Research and Development, 4(2), 71–79.

    PubMed  CAS  Google Scholar 

  • Krug, L. M., Kris, M. G., Rosenzweig, K., & Travis, W. D. (2008). Cancer of the lung. In V. T. DeVita Jr., S. Hellman, & S. A. Rosenberg (Eds.), Cancer: Principles & practice of oncology (8th ed., pp. 947–966). Philadelphia: Lippincott Williams Wilkins.

    Google Scholar 

  • Matlashewski, G., Lamb, P., Pim, D., Peacock, J., Crawford, L., & Benchimol, S. (1984). Isolation and characterization of a human p53 cDNA clone: Expression of the human p53 gene. EMBO Journal, 3(13), 3257–3262.

    PubMed  CAS  Google Scholar 

  • Mirza, A., McGuirk, M., Hockenberry, T. N., Wu, Q., Ashar, H., Black, S., Wen, S. F., Wang, L., Kirschmeier, P., Bishop, W. R., Nielsen, L. L., Pickett, C. B., & Liu, S. (2002). Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway. Oncogene, 21, 2613–2622.

    Article  PubMed  CAS  Google Scholar 

  • Mitsudomi, T., Hamajima, N., Ogawa, M., & Takahashi, T. (2000). Prognostic significance of p53 alterations in patients with non-small cell lung cancer: A meta-analysis. Clinical Cancer Research, 6, 4055–4063.

    PubMed  CAS  Google Scholar 

  • Moll, U. M., & Zaika, A. (2001). Nuclear and mitochondrial apoptotic pathways of p53. FEBS Letters, 493, 65–69.

    Article  PubMed  CAS  Google Scholar 

  • Nakano, J., Huang, C. L., Liu, D., Ueno, M., Sumitomo, S., & Yokomise, H. (2005). Survivin gene expression is negatively regulated by p53 tumor suppressor gene in non-small cell lung cancer. International Journal of Oncology, 27(5), 1215–1221.

    PubMed  CAS  Google Scholar 

  • Pietenpol, J. A., & Stewardt, Z. A. (2002). Cell cycle checkpoint signaling: Cell cycle arrest versus apoptosis. Toxicology, 181, 475–481.

    Article  PubMed  Google Scholar 

  • Pluquet, O., & Hainaut, P. (2001). Genotoxic and non-genotoxic pathways of p53 induction. Cancer Letters, 174, 1–15.

    Article  PubMed  CAS  Google Scholar 

  • Schmitt, C. A., Rosenthal, C. T., & Lowe, S. W. (2000). Genetic analysis of chemoresistance in primary murine lymphomas. Nature Medicine, 6(9), 1029–1035.

    Article  PubMed  CAS  Google Scholar 

  • Schuler, M., & Green, D. (2001). Mechanisms of p53-dependent apoptosis. Biochemical Society Transactions, 29, 36–42.

    Google Scholar 

  • Shert, T., Dy, G. K., & Adjei, A. (2008). Small cell lung cancer. Mayo Clinic Proceedings, 83(3), 355–367.

    Article  Google Scholar 

  • Skov, B. G., Holm, B., Erreboe, A., Skov, T., & Mellemgaard, A. (2010). ERCC1 and Ki-67 in small cell lung carcinoma and other neuroendocrine tumors of the lung: Distribution and impact on survival. Journal of Thoracic Oncology, 5(4), 453–459.

    Article  PubMed  Google Scholar 

  • Soomro, I. N., Holmes, J., & Whimster, W. F. (1998). Predicting prognosis in lung cancer: Use of proliferation marker, Ki-67 monoclonal antibody. The Journal of the Pakistan Medical Association, 48(3), 66–69.

    CAS  Google Scholar 

  • Tsao, A., & Glisson, B. (2006). Small cell lung cancer. In H. Kantarjian, R. Wolff, & C. Koller (Eds.), Anderson manual of medical oncology (pp. 233–256). New York: McGraw-Hill.

    Google Scholar 

  • Velculescu, V. E., Madden, S. L., Zhang, L., Lash, A. E., Yu, J., Rago, C., Lal, A., Wang, C. J., Beaudry, G. A., Ciriello, K. M., Cook, B. P., Dufault, M. R., Ferguson, A. T., Gao, Y., He, T. C., Hermeking, H., Hiraldo, S. K., Hwang, P. M., Lopez, M. A., Luderer, H. F., Mathews, B., Petroziello, J. M., Polyak, K., Zawel, L., & Kinzler, K. W. (1999). Analysis of human transcriptomes. Nature Genetics, 32, 387–388.

    Article  Google Scholar 

  • Wistuba, L., Gadzar, A. F., & Minna, J. D. (2001). Molecular genetics of small cell lung carcinoma. Seminars in Oncology, 28(Suppl 4), 3–13.

    Article  PubMed  CAS  Google Scholar 

  • Yamashita, S., Masuda, Y., Kurizaki, T., Haga, Y., Murayama, T., Ikei, S., Kamei, M., Takeno, S., & Kawahara, K. (2007). Survivin expression predicts early recurrence in early-stage breast cancer. Anticancer Research, 27, 2803–2808.

    PubMed  CAS  Google Scholar 

  • Yamashita, S., Chujo, M., Miyawaki, M., Tokuishi, K., Anami, K., Yamamoto, S., & Kawahar, K. (2009). Combination of p53AIP1 and survivin expression is a powerful prognostic marker in non-small cell lung cancer. Journal of Experimental & Clinical Cancer Research, 28(1), 22.

    Article  Google Scholar 

  • Yu, J., & Zhang, L. (2005). The transcriptional targets of p53 in apoptosis control. Biochemical and Biophysical Research Communications, 331, 851–858.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Supported by MZ 2007/48-UK-13 and VEGA 1/0050/11 Grants.

Conflicts of interest: The authors declare no conflicts of interest in relation to this article.

Author information

Authors and Affiliations

  1. Department of Medical Biology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Slovakia

    E. Halasova

  2. Institute of Histology and Embryology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Mala hora 4, Martin, SK-03754, Slovakia

    M. Adamkov & D. Dobrota

  3. Department of Medical Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Slovakia

    T. Matakova

  4. Department of Anatomy, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Slovakia

    D. Vybohova

  5. Department of Pharmacology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Slovakia

    M. Antosova

  6. Clinics of Stomatology and Maxillofacial Surgery, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and Faculty Hospital in Martin, Martin, Slovakia

    M. Janickova

  7. Department of Pathology, Hospital in Dolny Kubin, Dolby Kubin, Slovakia

    A. Singliar

  8. Department of Public Health, Jessenius Faculty of Medicine in Martin, Martin, Slovakia

    V. Jakusova

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  1. E. Halasova
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  2. M. Adamkov
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  7. A. Singliar
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  8. D. Dobrota
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  9. V. Jakusova
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Correspondence to M. Adamkov .

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Editors and Affiliations

  1. Medical Research Center, Respiratory Research, Polish Academy of Sciences, Pawinskiego 5, Warsaw, 02-106, Poland

    Mieczyslaw Pokorski

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Halasova, E. et al. (2013). Expression of Ki-67, Bcl-2, Survivin and p53 Proteins in Patients with Pulmonary Carcinoma. In: Pokorski, M. (eds) Respiratory Regulation - The Molecular Approach. Advances in Experimental Medicine and Biology, vol 756. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4549-0_3

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