Abnormal expression and its regulation mechanism of Cav-1 gene in gastric cancer / 临床与实验病理学杂志

ABSTRACT

Purpose To investigate the expression of Cav-1 in gastric cancer ( GC) cell lines and GC samples, and to analyze the pos-sible effect of gene methylation in expression of Cav-1. Methods Methylation specific PCR ( MSP) method was applied to examine the CpG methylation of the Cav-1 promoter in GC cell lines (AGS, MKN45, BGC-823) and 104 samples of GC and corresponding ad-jacent tissues. RT-PCR method was applied to examine the mRNA expression in GC cell lines. IHC were applied to examine the pro-tein expression of Cav-1 in the GC tissues. Results The expression level of Cav-1 mRNA was obviously increased after treated with 5-aza-2’-deoxycytidine (5-Aza-Dc, a demethylation agent) in AGS cell line. We detected the positive expression of Cav-1 gene in MKN45 and BGC-823 cell lines before and after treated with 5-Aza-Dc. The level of Cav-1 mRNA expression was no any change in AGS, MKN45 and BGC-823 cell lines treated with trichostatin A (TSA). MSP results showed that it can be amplified methylated bands in AGS cell line, and the methylated bands disappeared after treated with 5-Aza-Dc. MKN45 and BGC-823 cell lines were no any methylated bands amplified before and after treatment. The methylation frequency of Cav-1 gene was 29. 8% (31/104), which was significantly higher than that in adjacent tissues (P=0. 000). Furthermore, Cav-1 gene hypermethylation status was correlated with lymph node metastasis and family history of upper gastrointestinal cancers ( UGIC) , but not with pathological grade and clinical stage (P>0. 05). The positive frequency of Cav-1 expression was 51. 9%(54/104) in GC, which was significantly lower than that in adja-cent tissues (P=0. 000). The expression of Cav-1 was correlated with the frequency of gene methylation in GC tissues (P=0. 000). Conclusion The expression of Cav-1 was reduced in GC tissues and the gene hyermethylation may be one of the mechanisms causing Cav-1 gene silencing.