Epigenetic modification regulates both expression of tumor-associated genes and cell cycle progressing in human colon cancer cell lines: Colo-320 and SW1116  

作　　者：JingYuanFANG YingXuanCHEN JuanLU RongLU LiYANG HongYinZHU WeiQiGU LunGenLU 

机构地区：[1]ShanghaiInstituteofDigestiveDisease,RenjiHospitalShanghaiSecondMedicalUniversity,Shanghai200001,China.

出　　处：《Cell Research》2004年第3期217-226,共10页细胞研究（英文版）

基　　金：This work was supported in part by National Natural Science Foundation of China(No.30170413);the Foundation for Jing Yuan FANG of National Excellent Doctoral Dissertation of China(No.199946);the Foundation of Shanghai Education Committee(Shuguang Plan,No.02SG45).

摘　　要：The aim of this study is to assess the effects of DNA methylation and historic acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methyla-tion-specific PCR, and the acetylated status of the histones associated with the p21WAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry. We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73, c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.

关 键 词：human colon cancer cell lines tumor-associated genes DNA methylation histone acetylation cell cycle. 

分 类 号：Q279[生物学—细胞生物学]