Expression of Anti-apoptotic Protein Survivin and Tumor Suppressor P53 Protein in Patients with Pulmonary Carcinoma

Overview

Journal Eur J Med Res

Publisher Biomed Central

Specialty General Medicine

Date 2010 Feb 17

PMID 20156735

Authors

E Halasova

M Adamkov

E Kavcova

T Matakova

L Musak

D Vybohova

M Janickova

D Mistuna

A Singliar

Affiliations

Soon will be listed here.

Abstract

Background: Survivin is one of the inhibitors of the apoptosis gene family that has been implicated in both inhibition of apoptosis and mitosis regulation. p53 is one of the tumor suppressor genes; prevents tumor formation through cell cycle blocking and eliminates damaged cells via activation of apoptosis.

Objective: To investigate the possible regulation of survivin by p53, we examined the expression of both proteins in 67 patients with diagnosed lung cancer using immunohistochemical visualization.

Results: Survivin was predominantly expressed in both nucleus and cytoplasm, whereas p53 was expressed in the nucleus. There was a negative correlation between survivin and p53 expression. A decreased intensity of expression and fewer cells positive for survivin in small cell lung cancer in comparison with other lung cancer types were detected. There was no significant difference in the intensity of expression and the number of cells positive for p53 between small cell and non-small cell lung cancer types.

Conclusion: The present study suggests that survivin expression, as opposed to that of p53, is decreased in small cell lung cancer, which may differentiate this cancer from other lung cancer types other types.

References

Yamashita S, Chujo M, Miyawaki M, Tokuishi K, Anami K, Yamamoto S . Combination of p53AIP1 and survivin expression is a powerful prognostic marker in non-small cell lung cancer. J Exp Clin Cancer Res. 2009; 28:22. PMC: 2654787. DOI: 10.1186/1756-9966-28-22. View

Schuler M, Green D . Mechanisms of p53-dependent apoptosis. Biochem Soc Trans. 2001; 29(Pt 6):684-8. DOI: 10.1042/0300-5127:0290684. View

Yamashita S, Masuda Y, Kurizaki T, Haga Y, Murayama T, Ikei S . Survivin expression predicts early recurrence in early-stage breast cancer. Anticancer Res. 2007; 27(4C):2803-8. View

Deng Y, Wu X . Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria. Proc Natl Acad Sci U S A. 2000; 97(22):12050-5. PMC: 17292. DOI: 10.1073/pnas.97.22.12050. View

Pluquet O, Hainaut P . Genotoxic and non-genotoxic pathways of p53 induction. Cancer Lett. 2001; 174(1):1-15. DOI: 10.1016/s0304-3835(01)00698-x. View

Mitsudomi T, Hamajima N, Ogawa M, Takahashi T . Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. Clin Cancer Res. 2000; 6(10):4055-63. View

Akyurek N, Memis L, Ekinci O, Kokturk N, Ozturk C . Survivin expression in pre-invasive lesions and non-small cell lung carcinoma. Virchows Arch. 2006; 449(2):164-70. DOI: 10.1007/s00428-006-0239-9. View

Moll U, Zaika A . Nuclear and mitochondrial apoptotic pathways of p53. FEBS Lett. 2001; 493(2-3):65-9. DOI: 10.1016/s0014-5793(01)02284-0. View

Mirza A, McGuirk M, Hockenberry T, Wu Q, Ashar H, Black S . Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway. Oncogene. 2002; 21(17):2613-22. DOI: 10.1038/sj.onc.1205353. View

10.

Velculescu V, Madden S, Zhang L, Lash A, Yu J, Rago C . Analysis of human transcriptomes. Nat Genet. 1999; 23(4):387-8. DOI: 10.1038/70487. View

11.

Matlashewski G, Lamb P, Pim D, Peacock J, Crawford L, Benchimol S . Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene. EMBO J. 1984; 3(13):3257-62. PMC: 557846. DOI: 10.1002/j.1460-2075.1984.tb02287.x. View

12.

Jin Z, El-Deiry W . Overview of cell death signaling pathways. Cancer Biol Ther. 2005; 4(2):139-63. DOI: 10.4161/cbt.4.2.1508. View

13.

Fan J, Wang L, Jiang G, He W, Ding J . The role of survivin on overall survival of non-small cell lung cancer, a meta-analysis of published literatures. Lung Cancer. 2008; 61(1):91-6. DOI: 10.1016/j.lungcan.2007.11.011. View

14.

Yu J, Zhang L . The transcriptional targets of p53 in apoptosis control. Biochem Biophys Res Commun. 2005; 331(3):851-8. DOI: 10.1016/j.bbrc.2005.03.189. View

15.

Altieri D . Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 2003; 3(1):46-54. DOI: 10.1038/nrc968. View

16.

Pietenpol J, Stewart Z . Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis. Toxicology. 2002; 181-182:475-81. DOI: 10.1016/s0300-483x(02)00460-2. View

17.

Coutts A, La Thangue N . The p53 response during DNA damage: impact of transcriptional cofactors. Biochem Soc Symp. 2006; (73):181-9. DOI: 10.1042/bss0730181. View

18.

Kawasaki H, Altieri D, Lu C, Toyoda M, Tenjo T, Tanigawa N . Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res. 1998; 58(22):5071-4. View

19.

Nakano J, Huang C, Liu D, Ueno M, Sumitomo S, Yokomise H . Survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer. Int J Oncol. 2005; 27(5):1215-21. View

20.

Isobe M, Emanuel B, Givol D, Oren M, Croce C . Localization of gene for human p53 tumour antigen to band 17p13. Nature. 1986; 320(6057):84-5. DOI: 10.1038/320084a0. View