Differential 14-3-3 sigma DNA methylation and expression in c-myc- and activated H-ras-transformed cells under r- and K-selection.
We cloned rat 14-3-3 sigma, a mediator of p53 tumor suppressor, as a target of K-selection. 14-3-3 sigma expression is suppressed with DNA methylation in breast cancers while its overexpression with hypomethylation is frequent in pancreatic cancers. These opposite findings were recapitulated through r- and K-selection of transformed rat embryo fibroblasts. 14-3-3 sigma expression was suppressed with DNA methylation after r-selection and the gene was overexpressed and demethylated in K-selected cells. 5-aza-2'-deoxycytidine recovered 14-3-3 sigma expression in r-selected cells. The presence of heterogeneous methylation patterns and expression levels before selection suggests that different 14-3-3 sigma expression levels play a role as a prerequisite for selection and clonal evolution.
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Hiroyuki
H
Sato
Yukari
Y
Nakamura
Toru
T
Motokura
D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D019175:DNA Methylation; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D008957:Models, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014162:Transfection
D048948:14-3-3 Proteins; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016283:Proto-Oncogene Proteins p21(ras)