Aberrant hypermethylation of the FGFR2 gene in human gastric cancer cell lines

Department of Biochemistry and BK21 Center for Advanced Medical Education, Inha University School of Medicine, Incheon 400-712, Republic of Korea.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 07/2007; 357(4):1011-5. DOI: 10.1016/j.bbrc.2007.04.051
Source: PubMed

ABSTRACT We have previously shown that fibroblast growth factor receptor 2 (FGFR2) plays an important role in gastric carcinogenesis. In this study, we assessed DNA methylation status in the promoter region of FGFR2 gene in gastric cancer cell lines, and indicated that this region was highly methylated, compared with FGFR2-expressing gastric cancer cell lines. Moreover, the restoration of FGFR2 expression by treating methylated cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine strongly suggests that the loss of FGFR2 expression may be due to the aberrant hypermethylation in the promoter region of the FGFR2 gene. Thus, our results suggest that the epigenetic silencing of FGFR2 through DNA methylation in gastric cancer may contribute to tumor progression.

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    • "Overexpression of FGFR1 is commonly observed in diverse cancer cells, and this phenomenon has been indicated to arise from hypomethylation of CpG islands within the promoter region (Goldstein et al., 2007). FGFR2 has been shown to be silenced by promoter methylation in a number of cancers, including thyroid cancer, pituitary neoplasia, gastric cancer, and breast cancer, probably due to the need for tumors to avoid FGFR2's previously mentioned tumor-suppressive effect (Kondo et al., 2007a,b; Park et al., 2007; Zhu et al., 2007, 2010a,b). FGFR3 has also been found to be methylated in lung cancer but is expressed with a much lower methylation status in squamous cell carcinomas (Cortese et al., 2008), suggesting that FGFR3 may play different roles in different tumors. "
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    • "It has been observed that micro-RNAs are complementary to 3'UTR sequence motifs that regulate mRNA stability and mediate negative post-transcriptional regulation (Jackson, 1993; Lai, 2002). A recent study found that aberrant hypermethylation in the epigenetic silencing of the FGFR2 gene is related to human gastric cancer (Park et al., 2007). Further work would be required to determine whether either of these mechanisms is associated with endometriosis risk. "
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