Methylation and downregulated expression of mac25/insulin-like growth factor binding protein-7 is associated with liver tumorigenesis in SV40T/t antigen transgenic mice, screened by restriction landmark genomic scanning for methylation (RLGS-M).
Restriction landmark genomic scanning for methylation (RLGS-M) was used to detect alterations in DNA methylation associated with murine SV40 T/t antigen-induced hepatocarcinogenesis. An altered locus/spot (S130) was cloned and found to correspond to sequences in the 5' flanking region and 5' portion of the cDNA for the murine mac25/insulin-like growth factor binding protein-7 (Igfbp-7) gene. IGFBPs are believed to be capable of binding insulin, Igf1, and Igf2 and modulating mitogenic effects. Previous studies have shown that Igf2 has an important role in promoting liver tumorigenesis. Quantitative PCR was used to access the methylation status of the NotI site just 5' to the coding region and the expression level of the mac25/igfbp-7 gene. The results indicated that the degree of methylation was inversely related to the expression level and is consistent with a role for DNA methylation in silencing mac25/Igfbp-7 gene expression and function for mac25/Igfbp-7 as a tumor suppressor gene.
Komatsu
S
S
Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation, Tsukuba Life Science Center, Tsukuba, Ibaraki, Japan.
Okazaki
Y
Y
Tateno
M
M
Kawai
J
J
Konno
H
H
Kusakabe
M
M
Yoshiki
A
A
Muramatsu
M
M
Held
W A
WA
Hayashizaki
Y
Y
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D019175:DNA Methylation; D018076:DNA, Complementary; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D008113:Liver Neoplasms / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009115:Muridae; D015183:Restriction Mapping; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics*
D000952:Antigens, Polyomavirus Transforming; D002352:Carrier Proteins; D018076:DNA, Complementary; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1