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Hypermethylation patterns in the Fhit regulatory region are tissue specific
Author(s) -
Guler Gülnur,
Iliopoulos Dimitrios,
Han ShuangYin,
Fong Louise Y.Y.,
Lubet Ronald A.,
Grubbs Clinton J.,
Huebner Kay
Publication year - 2005
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20100
Subject(s) - fhit , dna methylation , biology , methylation , cancer research , intron , microbiology and biotechnology , carcinogen , carcinogenesis , gene expression , tumor suppressor gene , cancer , gene , genetics
DNA hypermethylation is associated with decreased expression of tumor suppressor genes. We previously observed decreased Fhit expression and Fhit promoter region hypermethylation in rodent tumors induced by various carcinogens, and noted that the 5′ regulatory regions in the promoter, exon 1, and intron 1 were differentially methylated, depending on the tissue of origin. Because different carcinogens were used for induction of tumors of the different organs, we could not conclude that the methylation patterns were tissue‐specific. To determine if in rat tissues: (1) Fhit methylation status is related to expression levels and (2) Fhit methylation patterns were tissue‐ or carcinogen‐specific, we examined Fhit methylation status and expression levels in DMBA‐ and MNU‐induced benign and malignant mammary tumors. Fhit intron 1 was methylated in 3/9 DMBA and all of MNU‐induced benign mammary tumors, in association with reduced Fhit expression levels; Fhit promoter and intron 1 were methylated in all DMBA and MNU‐induced carcinomas in association with highly reduced Fhit expression levels. Treatment of rat cancer cells in vitro with the DNA methyltransferase inhibitor, 5′‐Aza‐2′deoxycytidine, for 4 d, increased Fhit expression and altered the methylation status. Before treatment, both promoter and intron 1 regions were methylated; after treatment, only intron 1 remained methylated. Thus, in carcinogen‐exposed rat tissues there is an overall association of Fhit expression with regulatory region methylation, and hypermethylation patterns did not vary with carcinogen. The specific patterns of hypermethylated CpGs in the Fhit regulatory regions thus appear to be tissue‐specific. Published 2005 Wiley‐Liss, Inc.