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

Cervical cancer is a virus-induced disease that is caused by the integration of a human papilloma virus (HPV) DNA into the host's genome.^1-3

Infection with HPV causes disruption of the host's E2 gene, resulting in expression of viral oncogenes, E6 and E7.

The E6 and E7 products inhibit the activities of tumor suppressors, p53 and retinoblastoma protein, respectively.

This then eventually leads to the accumulation of damaged DNA and the development of cervical cancer.^4-5

Although cervical cancer is 1 of the causes of highest mortality in female cancer patients worldwide, it is a curable disease when diagnosed at an early stage.⁶

However, clear prognostic factors for cervical cancer development are not yet in existence.

Mitochondria, which are cell organelles involved in the processes of cell life and death and in tumoral transformation, appear to have prominent dysfunction in cancer cells.

Mitochondrial failure induces abnormal ultrastructures, deregulated metabolism, altered biochemistry and mutation of mitochondrial DNA (mtDNA) in cells.⁷

Mitochondrial molecular chaperones play important roles in protein transport, protein complex assembly, refolding of misfolded proteins and triggering of protein degradation by proteosomes.^8-9

Heat shock proteins (HSPs) are molecular chaperones that are classified into families according to their molecular weight (i.e., HSP100, HSP90, HSP70, HSP60, and small HPSs).

HSPs, an evolutionary conserved protein, are ubiquitous and have multiple functions in cellular homeo-stasis including gene expression regulation, DNA replication, signal transduction, differentiation, apoptosis, and cellular senescence or immortalization.

They also protect cells from various stresses such as hypoxia or ischemia, as well as sudden increases in temperature.^10-12

In normal cells, HSP60 is mostly localized in the mitochondrial matrix and outer mitochondrial membrane, constitutively expressed under normal condition, and induced by heat shock, mitochondrial damage, and mtDNA depletion.^13,14

Recently, other molecular roles for mammalian HSP60 have been reported. For example, human HSP60 may trigger apoptosis through caspase cascade activation by an association between HSP60/HSP10 complex and pro-caspase-3 inside the mitochondria, resulting in a subsequent release of the HSP60 into the cytoplasm.¹⁵

Overexpression of HSP60 has been reported in various tumors or cancers, such as adrenal Cushing tumors, human breast, large bowel, bronchial, exocervical, ovarian and prostate cancers.^16-23

Recently, an upregulation of HSP60 in preinvasive lesions of the cervix has been shown by immuhistochemistry.²⁴

Although HSP60 plays important roles in various biological events, the exact molecular roles of HSP60 are still poorly understood, and the relationship between HSP60 and invasive cervical cancer has not been reported yet.

In this study, we investigated the HSP60 expression in invasive cervical cancer tissues and evaluated any prognostic significance of HSP60 in cervical cancer using proteomics, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analyses.

Yonsei Med J. 2009 June 30; 50(3): 399–406.

Published online 2009 June 23. doi: 10.3349/ymj.2009.50.3.399.

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. 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 

SEE FULLTEXT

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2703764&tool=pmcentrez

http://www.e-medicum.com/noticiasDelDia/verNoticia.php?noticia=82912