genomic imprinting
The H19 locus acts in vivo as a tumor suppressor
02/09/2008
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.
PNAS 2008 105:12417-12422; published ahead of print August 21, 2008, doi:10.1073/pnas.0801540105
PNAS 2008 105:12417-12422; published ahead of print August 21, 2008, doi:10.1073/pnas.0801540105
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