Cancer Genetics and Epigenetics 2018, Vol.6, No.4, 25-32
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up-regulation of H19-IGF2 gene locus plays a role in the regulation of long-term hematopoietic stem cell function,
the down-regulation of hematopoietic stem cell activity and cell proliferation (Venkatraman et al., 2013).
Figure 2 PIK3/AKt and Ras/MAPK Pathway Diagrams (The Signaling Pathway of PIK3/AKt and Ras/MAPK (Massoner et al.,
2010))
2 Cloning and Expression of IGF2 Gene
Using the identical sequences of IGF1 and IGF2 as probes, Bell et al. cloned IGF2 from human liver DNA Library
in 1984 and deduced a 180-amino-acid IGF2 protein precursor, which contains N-terminal signal sequence
followed by mature peptide and C-terminal extension, i.e. E region. Both signal sequence and D region were
hydrolyzed by proteins and then migrated to form mature 67 amino acid peptide. A Buffalo rat liver IGF2 gene
was used as a probe. Dull et al. cloned human IGF2 from human embryonic liver gene library in the same year. It
is inferred that the precursor of IGF2 of 180 amino acids starts at the middle 24 and its molecular weight is 20.1
kD (Williams et al., 2013). Using the coding region of human liver IGF2 as a probe, Shen et al. cloned IGF2 from
human embryonic DNA Library in 1988. They identified four embryonic variants, different from liver variants,
with only 5’end primers and nearly identical coding sequences. RNA imprinting analysis revealed transcripts 6.0,
4.9 and 3.2 kb in embryos using special exon probes. The 4.9 KB variant at the 5-terminal is different from the
liver transcript and other embryonic transcripts.
De Pagter-Holthuizen et al. (1987) elucidated that 5.3-kb mRNA originated in exon 1 of IGF2 and expressed in
adult liver, while 6.0-kb transcript originated in exon 4 and expressed in embryonic tissues and some adult
non-liver tissues. They concluded that the 2.2-kb transcript also started at exon 4. 4.8-kb transcript originates from
exon 4B, which is expressed in most embryonic tissues and some adult non-liver tissues. RNA imprinting analysis
using a 3’-terminal primer UTR probe revealed an abnormal 1.8-kb transcript in the liver of adults and embryos,
adrenal glands, skeletal muscles and kidneys of embryos, but not in the lungs and brain tissues of embryos.
