Aberrant methylation of integrin alpha4 gene in human gastric cancer cells.
Integrins are adhesion receptors that mediate both cell-extracellular matrix and cell-cell interactions. It has also been reported that the loss of integrin alpha4 expression might be associated with metastasis in several cancers. However, the molecular mechanism for loss of their expression in cancers has not been explored. In the present study, we found that the integrin alpha4 expression is lost in human gastric cancer cell lines and that this is recovered by treatment with DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. Methylation-specific PCR (MSP) and bisulfite genomic DNA sequencing demonstrated the CpG methylation-dependent silencing of integrin alpha4 expression in eight of nine (88.8%) gastric cancer cell lines and in 84.7% of 46 primary tumors. We also investigated whether the restoration of integrin alpha4 in integrin alpha4-inactivated cells affects their ability to invade extracellular matrix, using matrigel assays. Interestingly, integrin alpha4-stable transfectants had markedly less invasive ability than the parental cells. Taken together, these results suggest that the transcriptional repression of the integrin alpha4 gene is caused by aberrant DNA methylation, and that this may play an important role in human gastric carcinogenesis.
National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea.
Jinah
J
Park
Sang-Hyun
SH
Song
Tai Young
TY
Kim
Moon-Chang
MC
Choi
Hyun-Soon
HS
Jong
Tae-You
TY
Kim
Jung Weon
JW
Lee
Noe Kyeong
NK
Kim
Woo-Ho
WH
Kim
Yung-Jue
YJ
Bang
D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D039441:Integrin alpha4 / Q000235:genetics*; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology
D039441:Integrin alpha4