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Yonsei Med J. 2009 Jun;50(3):399-406.
Published online 2009 June 23.  doi: 10.3349/ymj.2009.50.3.399.
© Copyright: Yonsei University College of Medicine 2009
Expression of Heat Shock Protein 60 kDa Is Upregulated in Cervical Cancer
You Jin Hwang,1 Soon Pyo Lee,2 Suk Young Kim,2 Young Hwan Choi,1 Min Ji Kim,1 Choong Ho Lee,1 Joo Young Lee,3 and Dae Young Kim1
1Division of Biological Science, Gachon University of Medicine and Science, Incheon, Korea.
2Department of Obstetrics and Gynecology, Gachon University of Medicine and Science, Incheon, Korea.
3Department of Pharmacology, Korea University College of Medicine, Seoul, Korea.

Corresponding author: Dr. Dae Young Kim, Divison of Biological Science, Gachon University of Medicine and Science, 534-2 Yeonsu-dong, Yeonsu-gu, Incheon 406-799, Korea. Tel: 82-32-820-4544, Fax: 82-32-821-2734, Email: davekim@gachon.ac.kr
Received May 22, 2008; Revised September 04, 2008; Accepted October 01, 2008.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract

Purpose

Cervical cancer caused by the human papilloma virus (HPV) continues to be the cause of yearly death among women. However, it is a curable disease when diagnosed at an early stage. Recently, several researches have reported that heat shock protein (HSP) 60, a chaperone protein of molecular weight of 60 kDa, is involved in carcinogenesis and apoptosis. In order to evaluate the prognostic significance of HSP60 in cervical cancer, we examined differences in the HSP60 expression between cervical cancer and normal tissues in women.

Materials and Methods

Tissue samples were collected from 20 cervical cancer patients and 20 normal controls. HSP60 expression of cervical cancer and normal tissues were verified by the 2D gel proteomics, semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analyses.

Results

In 2D proteomic analysis, an increase of HSP60 expression was detected in cervical cancer tissues and confirmed by Western blot analysis (p < 0.05). However, messenger RNA (mRNA) levels of HSP60 did not display any significant differences between cervical cancer and normal tissues.

Conclusion

These results suggest that HSP60 may be involved in the development of cervical cancer and have profound biological and prognostic significance.

Keywords: Heak shock protein, cervical cancer, prognostic marker.
References
1. Bosch FX,Manos MM,Muhoz N,Sherman M,Jansen AM,Peto J,et al. International biological study on cervical cancer (IBSCC) Study Group. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst 1995;87:796–802.
2. Walboomers JM,Jacobs MV,Manos MM,Bosch FX,Kummer JA,Shah KV,et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12–19.
3. Munoz N,Bosch FX,de Sanjosé S,Herrero R,Castellsagué X,Shah KV,et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518–527.
4. Klaes R,Woerner SM,Ridder R,Wentzensen N,Duerst M,Schneider A,et al. Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes. Cancer Res 1999;59:6132–6136.
5. Furumoto H,Irahara M. Human papilloma virus (HPV) and cervical cancer. J Med Invest 2002;49:124–133.
6. Charvet I,Meda P,Genet M,Pelte MF,Vlastos AT. [Optical diagnosis of cervical dysplasia]. Bull Cancer 2004;91:45–53.
7. Czarnecka AM,Campanella C,Zummo G,Cappello F. Mitochondrial chaperones in cancer: from molecular biology to clinical diagnostics. Cancer Biol Ther 2006;5:714–720.
8. Höhfeld J,Cyr DM,Patterson C. From the cradle to the grave: molecular chaperones that may choose between folding and degradation. EMBO Rep 2001;2:885–890.
9. Eng C,Kiuru M,Fernandez MJ,Aaltonen LA. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer 2003;3:193–202.
10. Srivastava PK,Maki RG. Stress-induced proteins in immune response to cancer. Curr Top Microbiol Immunol 1991;167:109–123.
11. Ellis RJ. Molecular chaperones: pathways and networks. Curr Biol 1999;9:R137–R139.
12. Jolly C,Morimoto RI. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 2000;92:1564–1572.
13. Soltys BJ,Gupta RS. Mitochondrial-matrix proteins at unexpected locations: are they exported?. Trends Biochem Sci 1999;24:174–177.
14. Hansen JJ,Bross P,Westergaard M,Nielsen MN,Eiberg H,Børglum AD,et al. Genomic structure of the human mitochondrial chaperonin genes: HSP60 and HSP10 are localised head to head on chromosome 2 separated by a bidirectional promoter. Hum Genet 2003;112:71–77.
15. Samali A,Cai J,Zhivotovsky B,Jones DP,Orrenius S. Presence of a pre-apototic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells. EMBO J 1999;18:2040–2048.
16. Bini L,Magi B,Marzocchi B,Arcuri F,Tripodi S,Cintorino M,et al. Protein expression profiles in human breast ductal carcinoma and histologically normal tissue. Electrophoresis 1997;18:2832–2841.
17. Schneidér J,Jimenez E,Marenbach K,Romero H,Mark D,Meden H. Immunohistochemical detection of HSP60-expression in human ovarian cancer. Correlation with survival in a series of 247 patients. Anticancer Res 1999;19:2141–2146.
18. Cappello F,Bellafiore M,Palma A,Marciano V,Martorana G,Belfiore P,et al. Expression of 60-kD heat shock protein increases during carcinogenesis in the uterine exocervix. Pathobiology 2002-2003;70:83–88.
19. Cappello F,Bellafiore M,Palma A,David S,Marcianó V,Bartolotta T,et al. 60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis. Eur J Histochem 2003;47:105–110.
20. Cappello F,Rappa F,David S,Anzalone R,Zummo G. Immunohistochemical evaluation of PCNA, p53, HSP60, HSP10 and MUC-2 presence and expression in prostate carcinogenesis. Anticancer Res 2003;23:1325–1331.
21. Pignatelli D,Ferreira J,Soares P,Costa MJ,Magalhaes MC. Immunohistochemical study of heat shock proteins 27, 60 and 70 in the normal human adrenal and in adrenal tumors with suppressed ACTH production. Microsc Res Tech 2003;61:315–323.
22. Cappello F,David S,Rappa F,Bucchieri F,Marasá L,Bartolotta TE,et al. The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer 2005;5:139.
23. Cappello F,Di Stefano A,D'Anna SE,Donner CF,Zummo G. Immunopositivity of heat shock protein 60 as a biomarker of bronchial carcinogenesis. Lancet Oncol 2005;6:816.
24. Castle PE,Ashfaq R,Ansari F,Muller CY. Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix. Cancer Lett 2005;229:245–252.
25. Kim JY,Shin HJ,Kim TH,Cho KH,Shin KH,Kim BK,et al. Tumor-associated carbonic anhydrases are linked to metastases in primary cervical cancer. J Cancer Res Clin Oncol 2006;132:302–308.
26. Matsui NM,Smith-Beckerman DM,Epstein LB. Staining of preparative 2-D gels. Coomassie blue and imidazole-zinc negative staining. Methods Mol Biol 1999;112:307–311.
27. Cornford PA,Dodson AR,Parsons KF,Desmond AD,Woolfenden A,Fordham M,et al. Heat Shock Protein Expression Independently predicts clinical outcome in prostate cancer. Cancer Res 2000;60:7099–7105.
28. Kirchhoff SR,Gupta S,Knowlton AA. Cytosolic heat shock protein 60, apoptosis, and myocardial injury. Circulation 2002;105:2899–2904.
29. Cappello F,Di Stefano A,David S,Rappa F,Anzalone R,La Rocca G,et al. Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease. Cancer 2006;107:2417–2424.
30. Kimura E,Enns RE,Alcaraz JE,Arboleda J,Slamon DJ,Howell SB. Correlation of the survival of ovarian cancer patients with mRNA expression of the 60-kD heat-shock protein HSP-60. J Clin Oncol 1993;11:891–898.
31. Chant ID,Rose PE,Morris AG. Analysis of heat-shock protein expression in myeloid leukemia cells by flow cytometry. Br J Haematol 1995;90:163–168.
32. Franzén B,Linder S,Alaiya AA,Eriksson E,Fujioka K,Berman AC,et al. Analysis of polypeptide expression in benign and malignant human breast lesions. Electrophoresis 1997;18:582–587.