Open AccessThe H19 locus acts in vivo as a tumor suppressor
Author(s) -
Tomomi Yoshimizu,
Audrey Miroglio,
MarieAnne Ripoche,
Anne Gabory,
Maria Vernucci,
Andrea Riccio,
Sabine Colnot,
Cécile Godard,
Benoı̂t Terris,
Hélène Jammes,
Luisa Dandolo
Publication year - 2008
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0801540105
Subject(s) - locus (genetics) , carcinogenesis , tumor suppressor gene , biology , suppressor , genomic imprinting , cancer research , gene , oncogene , imprinting (psychology) , loss of heterozygosity , genetics , dna methylation , gene expression , allele , cell cycle
The H19 locus belongs to a cluster of imprinted genes that is linked to the human Beckwith-Wiedemann syndrome. The expression of H19 and its closely associated IGF2 gene is frequently deregulated in some human tumors, such as Wilms' tumors. In these cases, biallelic IGF2 expression and lack of expression of H19 are associated with hypermethylation of the imprinting center of this locus. These observations and others have suggested a potential tumor suppressor effect of the H19 locus. Some studies have also suggested that H19 is an oncogene, based on tissue culture systems. We show, using in vivo murine models of tumorigenesis, that the H19 locus controls the size of experimental teratocarcinomas, the number of polyps in the Apc murine model of colorectal cancer and the timing of appearance of SV40-induced hepatocarcinomas. The H19 locus thus clearly displays a tumor suppressor effect in mice.
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