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High frequency methylation of p16INK4A gene during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.
- Source :
-
Oncology reports [Oncol Rep] 2004 Jul; Vol. 12 (1), pp. 101-6. - Publication Year :
- 2004
-
Abstract
- The p16INK4A tumor suppressor gene can be inactivated by hypermethylation of the promoter region in many type of tumors including oral cancer. We recently studied the relationship of inactivation of p16INK4A and tumorigenesis in oral cancer. The aim of the present study was to describe the relationship between macroscopic changes of rat oral mucosa treated with 4-nitroquinoline 1-oxide (4NQO) and an inactivation of p16INK4A. We analyzed the relation of p16INK4A inactivation by hypermethylation of the promoter region of p16INK4A gene using polymerase chain reaction (PCR), PCR-single-strand confirmation polymorphism (PCR-SSCP), and methylation-specific-PCR (MSP). We observed that methylation of p16INK4A genes were rare in mild and moderate dysplasia, but inactivation was observed at high frequency even in severe dysplasia and SCCs in rat carcinogenesis. The expression pattern of p16INK4A protein, detected by western blotting and immunohistochemistry, were similar to the hypermethylation status of the p16INK4A promoter region. Inactivation by hypermethylation of the promoter region of p16INK4A gene was related to carcinogenesis of oral cancer.
- Subjects :
- Animals
Base Sequence
Carcinogens
Carcinoma, Squamous Cell chemically induced
Carcinoma, Squamous Cell pathology
DNA Primers
DNA, Neoplasm genetics
Exons genetics
Loss of Heterozygosity
Mouth Mucosa drug effects
Mouth Mucosa pathology
Rats
Tongue Neoplasms chemically induced
Tongue Neoplasms pathology
4-Nitroquinoline-1-oxide toxicity
Carcinoma, Squamous Cell genetics
Cyclin-Dependent Kinase Inhibitor p16 genetics
DNA Methylation
Tongue Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1021-335X
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 15201967