Methylation status of genes upregulated by demethylating agent 5-aza-2′-deoxycytidine in hepatocellular carcinoma

被引：61

作者：

Hirasawa, Yuichi

Arai, Makoto

Imazeki, Fumio

Tada, Motohisa

Mikata, Rintaro

Fukai, Kenichi

Miyazaki, Masaru

Ochiai, Takenori

Saisho, Hiromitsu

Yokosuka, Osamu

机构：

[1] Chiba Univ, Grad Sch Med, Dept Med & Clin Oncol K1, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Century Ctr Excellence Program 21, Chiba 2608670, Japan

[3] Chiba Univ, Grad Sch Med, Dept Gen Surg, Chiba 2608670, Japan

[4] Chiba Univ, Grad Sch Med, Dept Acad Surg, Chiba 2608670, Japan

来源：

ONCOLOGY | 2006年 / 71卷 / 1-2期

关键词：

methylation; hepatocellular carcinoma; cysteine and glycine-rich protein 1; caveolin; 1;

D O I：

10.1159/000100475

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aims: To determine the clinical significance of gene promoter methylation in hepatocellular carcinoma (HCC), we examined in clinical samples the methylation status of those promoters that showed elevated activity in hepatoma cell lines after 5-aza-2'-deoxycytidine treatment. Methods: Regarding the genes with promoter hypermethylation in the cell lines, their expression levels and methylation status in HCC and non-HCC tissues were assessed by semiquantitive RT-PCR and methylation-specific PCR. To confirm the result, the expression levels and methylation status in 16 additional HCC and non-HCC tissues were assessed. Results: The promoter regions of caveolin 1 (CAV1), cysteine and glycine-rich protein 1 (CSRP1), Kruppel-like factor 6 (KLF6), myosin (light polypeptide 9) (MYL9), and transgelin (TAGLN) were highly methylated in the cell lines. CAV1 and CSRP1 were methylated in HCC more frequently than in non-HCC. KLF6, MYL9, and TAGLN were fully methylated in both HCC and non-HCC. Using additional clinical samples, down-regulation of CAV1 and CSRP1 was observed in 38 and 56%, respectively, of the 16 HCC samples and aberrant methylation of CAV1 and CSRP1 was observed in 56% of HCC in both cases. Conclusion: CAV1 and CSRP1 were inactivated in HCC by aberrant methylation and they may serve as important biomarkers of malignancy.

引用

页码：77 / 85

页数：9

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