Reference SummaryTakagi H, Cancer Res 1992 Oct 1;52(19):5171-7

Title

Molecular and genetic analysis of liver oncogenesis in transforming growth factor alpha transgenic mice.

Authors

Takagi H; Sharp R; Hammermeister C; Goodrow T; Bradley MO; Fausto N; Merlino G

Journal

Cancer Res

Volume

52

Issue

19

Year

1992

Pages

5171-7

Abstract

Overexpression of a transforming growth factor alpha (TGF-alpha) transgene induced the development of liver tumors in 69 of 93 (74%) adult male mice. To identify factors associated with oncogenesis, liver tumors from transgenic animals were characterized at the molecular level. TGF-alpha RNA transcripts were elevated in 17 of 25 (68%) liver tumors, relative to adjacent nontumorous tissue. Expression of the endogenous c-myc and insulin-like growth factor II genes was enhanced in 7 of 19 (37%) and 12 of 16 (75%) tumors, respectively. In contrast, epidermal growth factor receptor RNA levels were unchanged or reduced in all liver tumors, and mutations were not detected in either the Ha-ras or Ki-ras genes. The occurrence of liver tumors in castrated TGF-alpha transgenic mice was reduced about 7-fold, while in ovariectomized transgenic animals the incidence was increased about 6-fold. The progeny of a cross between CD1-derived TGF-alpha transgenic (MT42) and C57BL/6 mice exhibited no reduction in tumor burden (83%); however, the incidence of tumor formation in MT42 x FVB/N offspring was substantially lower (19%). We conclude that in these transgenic mice TGF-alpha promotes tumor formation and appears to play a major role in tumor progression. Moreover, other factors that may collaborate in TGF-alpha-induced hepatocarcinogenesis include c-myc, insulin-like growth factor II, sex hormones, and the genetic background upon which the transgene operates.

Links

J:2578 – MGI References
1394122 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6;CD-1-Tg(MtTGFA)42Lmb Hemizygous mice were used in these experiments.
The genetic background of these mice is mixed C57BL/6J and CD-1. Transgenic mice on a CD-1 background had been backcrossed 2 times to C57BL/6.
C57BL/6J Inbred mice from the Jackson Laboratory.
CD-1-Tg(MtTGFA)42Lmb Results were combined for transgenic mice that were either hemizygous or homozygous.
The transgene was expressed in the liver of both intact and castrated mice.
FVB;CD-1-Tg(MtTGFA)42Lmb Hemizygous mice.
The genetic background of these mice is mixed C57BL/6J and FVB/NHsd.
Visual Summary Grid

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular adenoma Liver

observed

CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular adenoma
  • ZnSO4
  • castration
Liver

10

CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular adenoma
  • (see notes)
Liver

very low

CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma Liver

observed

CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma
  • ZnSO4
Liver

0 - 43

CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma
  • ZnSO4
  • castration
Liver

0

CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma
  • (see notes)
Liver

0

CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma
  • ZnSO4
  • testosterone
  • ovariectomy
Liver

50

CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma
  • ZnSO4
  • ovariectomy
Liver

14

B6;CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma Liver

67

FVB;CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma
  • (see notes)
Liver

0

CD-1-Tg(MtTGFA)42Lmb Liver tumor
  • (see notes)
Liver

very low - 74

CD-1-Tg(MtTGFA)42Lmb Liver tumor
  • ZnSO4
Liver

11 - 86

CD-1-Tg(MtTGFA)42Lmb Liver tumor Liver

62

CD-1-Tg(MtTGFA)42Lmb Liver tumor
  • ZnSO4
  • castration
Liver

10

CD-1-Tg(MtTGFA)42Lmb Liver tumor
  • ZnSO4
  • ovariectomy
Liver

57

CD-1-Tg(MtTGFA)42Lmb Liver tumor
  • ZnSO4
  • testosterone
  • ovariectomy
Liver

67

CD-1 Liver tumor
  • (see notes)
Liver

0 - 4.8

CD-1 Liver tumor
  • ZnSO4
Liver

0

CD-1 Liver tumor
  • ZnSO4
  • castration
Liver

0

CD-1 Liver tumor
  • ZnSO4
  • ovariectomy
Liver

0

CD-1 Liver tumor
  • ZnSO4
  • testosterone
  • ovariectomy
Liver

0

B6;CD-1-Tg(MtTGFA)42Lmb Liver tumor Liver

83

FVB;CD-1-Tg(MtTGFA)42Lmb Liver tumor
  • (see notes)
Liver

19

FVB/NHsd Liver tumor Liver

0

C57BL/6J Liver tumor Liver

low