Gene amplification and expression of the DNA repair enzyme, N-methylpurine-DNA glycosylase (MPG) in HPV-infected cervical neoplasias.

Abstract

BACKGROUND:

Lethal and mutagenic damages of DNA is caused by a variety of agents including viruses. It is known that HPV is one of the major causes of cervical carcinogenesis and that cells eliminate DNA lesions with DNA repair enzymes. However, the role of N-methylpurine-DNA glycosylase (MPG) is not known in the development of cervical cancer.

MATERIALS AND METHODS:

Multiplex polymerase chain reaction (PCR) was used for the detection and typing of HPV in the biopsy. Gene amplification of MPG was measured by a PCR-based assay. The mRNA levels of MPG were determined by reverse transcription-PCR using hypoxanthine-guanine phosphoribosyl transferase as the reference gene. An immunohistochemical technique was used to examine the distribution of MPG in the tissues.

RESULTS:

Of 68 Korean cervical neoplasia patients, 86.8% showed HPV infection. High-risk HPV 16/18 were the most prevalent but positive only in 47.3% of the invasive cancer patients. Gene amplification of MPG was significantly increased in high-risk HPV-infected tissues as compared to low-risk HPV-infected and normal tissues (p < 0.05). The mRNA levels of MPG were higher in HPV-infected invasive carcinoma than normal cervical tissues. Immunohistochemical staining revealed that the intracellular expression and distribution (localization) of MPG altered in the cervical neoplasia. Interestingly, MPG expression in CIN III and invasive carcinoma (IC) was much higher than normal and CIN I. Granular positivity of MPG was notable in the perinuclear regions of the cytoplasm in HPV-infected invasive cancer.

CONCLUSION:

This is the first report on MPG expression in cervical neoplasia. Our results indicate that the gene amplification and expression of MPG were increased in high-risk HPV-infected cervical neoplasias and the intracellular distribution of MPG protein was altered, suggesting a role of MPG in carcinogenesis.

• Authors: T J Sohn, N K Kim, H J An, J J Ko, T R Hahn, D Oh, S G Lee, R Roy, K Y Cha, Y K Oh
• Journal: Anticancer research (Anticancer Res) 2001 Jul-Aug Vol. 21 Issue 4A Pg. 2405-11 ISSN: 0250-7005 [Print] Greece
• PMID: 11724299 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• DNA Glycosylases
• N-Glycosyl Hydrolases
• DNA-3-methyladenine glycosidase II

Topics

• DNA Glycosylases
• DNA Repair (physiology)
• Female
• Gene Amplification
• Humans
• Intracellular Fluid (enzymology)
• N-Glycosyl Hydrolases (biosynthesis, genetics)
• Papillomaviridae (genetics)
• Papillomavirus Infections (complications, enzymology, epidemiology)
• Prevalence
• RNA, Messenger (biosynthesis, genetics)
• Tumor Virus Infections (complications, enzymology, epidemiology)
• Uterine Cervical Neoplasms (enzymology, genetics, virology)
• Uterine Cervical Dysplasia (enzymology, genetics, virology)