title: Multiple regulatory mechanisms of hepatocyte growth factor expression in malignant cells with a short poly(dA) sequence in the HGF gene promoter.
abstract: Hepatocyte growth factor (HGF) expression is a poor prognostic factor in various types of cancer. Expression levels of HGF have been reported to be regulated by shorter poly(dA) sequences in the promoter region. In the present study, the poly(dA) mononucleotide tract in various types of human cancer cell lines was examined and compared with the HGF expression levels in those cells. Short deoxyadenosine repeat sequences were detected in five of the 55 cell lines used in the present study. The H69, IM95, CCK-81, Sui73 and H28 cells exhibited a truncated poly(dA) sequence in which the number of poly(dA) repeats was reduced by ≥5 bp. Two of the cell lines exhibited high HGF expression, determined by reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The CCK-81, Sui73 and H28 cells with shorter poly(dA) sequences exhibited low HGF expression. The cause of the suppression of HGF expression in the CCK-81, Sui73 and H28 cells was clarified by two approaches, suppression by methylation and single nucleotide polymorphisms in theHGFgene. Exposure to 5-Aza-dC, an inhibitor of DNA methyltransferase 1, induced an increased expression of HGF in the CCK-81 cells, but not in the other cells. Single-nucleotide polymorphism (SNP) rs72525097 in intron 1 was detected in the Sui73 and H28 cells. Taken together, it was found that the defect of poly(dA) in theHGFpromoter was present in various types of cancer, including lung, stomach, colorectal, pancreas and mesothelioma. The present study proposes the negative regulation mechanisms by methylation and SNP in intron 1 ofHGFfor HGF expression in cancer cells with short poly(dA).
authors.affiliation: Department of Genome Biology, Faculty of Medicine, Kinki University, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Kinki University, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Center for Clinical and Translational Research, Kyushu University Hospital, Fukoka, Kyushu 812-8581, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Kinki University, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Genome Biology, Faculty of Medicine, Kinki University, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
keywords: cancer; deletion; hepatocyte growth factor; methylation; poly(dA)