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Effects of DNA Methylation on Expression of Tumor Suppressor Genes and Proto-oncogene in Human Colon Cancer Cell Lines

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Specialty Gastroenterology
Date 2003 Sep 13
PMID 12970888
Citations 11
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Abstract

Aim: To investigate the effects of DNA methylation on the expression of tumor suppressor genes and proto-oncogene in human colon cancer cell lines.

Methods: Three colon cancer cell lines (HT-29, SW1116 and Colo-320) treated with different concentrations of DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC) were used to induce DNA demethylation. The expressions of p16(INK4A), p21(WAF1), APC and c-myc genes were observed by using RT-PCR. The methylation status of p16(INK4A) promoter in HT-29 cells was also determined by methylation-specific PCR (MSP).

Results: Weak expressions of p16(INK4A) and APC in the three colon cancer cells were detected, and p21(WAF1) expression was not found in SW1116 and Colo-320 cells before treatment. After treatment of 1 micromol/L but not 10 micromol/L of 5-aza-dC, the methylation level of p16(INK4A) gene promoter decreased significantly, and the hypomethylation led to the up-regulation of p16(INK4A) gene transcription in HT-29 cells. In the cell lines of SW1116 and Colo-320, p16(INK4A) and APC mRNA expressions were obviously enhanced after treatment of either 10 micromol/L or 5 micromol/L 5-aza-dC for 24 h. However, no evidence was found that methylation regulated the expression of p21(WAF1) and c-myc genes in human colon cancer cell lines.

Conclusion: Expression of p16(INK4A) and APC genes is regulated by DNA methylation in three human colon cancer cell lines.

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References
1.
Grant P, Hebbes T, Allis C, Workman J . Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro. EMBO J. 1996; 15(10):2508-18. PMC: 450183. View

2.
Allan L, Duhig T, Read M, Fried M . The p21(WAF1/CIP1) promoter is methylated in Rat-1 cells: stable restoration of p53-dependent p21(WAF1/CIP1) expression after transfection of a genomic clone containing the p21(WAF1/CIP1) gene. Mol Cell Biol. 2000; 20(4):1291-8. PMC: 85267. DOI: 10.1128/MCB.20.4.1291-1298.2000. View

3.
Abele R, Clavel M, Dodion P, Bruntsch U, Gundersen S, Smyth J . The EORTC Early Clinical Trials Cooperative Group experience with 5-aza-2'-deoxycytidine (NSC 127716) in patients with colo-rectal, head and neck, renal carcinomas and malignant melanomas. Eur J Cancer Clin Oncol. 1987; 23(12):1921-4. DOI: 10.1016/0277-5379(87)90060-5. View

4.
Bellet R, Mastrangelo M, Engstrom P, STRAWITZ J, Weiss A, Yarbro J . Clinical trial with subcutaneously administered 5-azacytidine (NSC-102816). Cancer Chemother Rep. 1974; 58(2):217-22. View

5.
Clark S, Harrison J, Paul C, Frommer M . High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 1994; 22(15):2990-7. PMC: 310266. DOI: 10.1093/nar/22.15.2990. View