The H19 locus acts in vivo as a tumor suppressor.
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.
Yoshimizu
Tomomi
T
Department of Genetics and Development, Institut Cochin, University Paris Descartes, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut National de la Santé et de la Recherche Médicale U567, Paris 75014, France.
Miroglio
Audrey
A
Ripoche
Marie-Anne
MA
Gabory
Anne
A
Vernucci
Maria
M
Riccio
Andrea
A
Colnot
Sabine
S
Godard
Cécile
C
Terris
Benoit
B
Jammes
Hélène
H
Dandolo
Luisa
L
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D015179:Colorectal Neoplasms / Q000473:pathology; D004195:Disease Models, Animal; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D007335:Insulin-Like Growth Factor II; D051379:Mice; D008817:Mice, Mutant Strains; D005810:Multigene Family; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000145:classification / Q000502:physiology*; D013724:Teratoma / Q000473:pathology
C094335:H19 long non-coding RNA; C513121:IGF2 protein, mouse; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II