Reactivation of the maternally imprinted IGF2 allele in TGFα induced hepatocellular carcinomas in mice

Thomas M. Harris, Leslie E. Rogler, Charles E. Rogler

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The Insulin like growth factor 2 (IGF2) gene is expressed in several types of tumors in humans and mice and has been implicated as an important growth factor in tumor progression. IGF2 expression in the TGFα transgenic mice was analysed in liver and tumors from animals which also contained one or two functional IGF2 alleles. In a two by two mating experiment using transgenic mice containing either a TGFα transgene or a IGF2 gene knockout, we have investigated whether IGF2 imprinting is reversed during hepatocarcinogenesis and the consequences of IGF2 expression for tumor growth. We observed that: (1) 100% of the hepatocellular carcinomas expressed IGF2 (2) the normally imprinted maternal allele is active in the tumors in which the paternal allele is knocked out and (3) all three of the murine IGF2 promoters upstream of the reactivated maternal alleles are transcriptionally active in tumors. We also observed that the total tumor burden of animals with two wild type IGF-2 alleles (paternal and maternal) was the same as the tumor burden in animals which contained only a single reactivated maternal allele. The 100% incidence of reactivation of the imprinted maternal allele suggests that IGF2 expression is selected during murine hepatocarcinogenesis and can substitute for the paternal allele when it is inactivated.

Original languageEnglish (US)
Pages (from-to)203-209
Number of pages7
JournalOncogene
Volume16
Issue number2
StatePublished - Jan 15 1998

Fingerprint

Somatomedins
Hepatocellular Carcinoma
Alleles
Mothers
Neoplasms
Tumor Burden
Transgenic Mice
Gene Knockout Techniques
Insulin-Like Growth Factor II
Transgenes
Intercellular Signaling Peptides and Proteins
Liver
Incidence
Growth

Keywords

  • DEN
  • Hepatocellular carcinoma
  • IGF2
  • Imprinting
  • Transgenic mice

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Reactivation of the maternally imprinted IGF2 allele in TGFα induced hepatocellular carcinomas in mice. / Harris, Thomas M.; Rogler, Leslie E.; Rogler, Charles E.

In: Oncogene, Vol. 16, No. 2, 15.01.1998, p. 203-209.

Research output: Contribution to journalArticle

Harris, Thomas M. ; Rogler, Leslie E. ; Rogler, Charles E. / Reactivation of the maternally imprinted IGF2 allele in TGFα induced hepatocellular carcinomas in mice. In: Oncogene. 1998 ; Vol. 16, No. 2. pp. 203-209.
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