Reference SummaryHansen LA, Carcinogenesis 1996 Sep;17(9):1825-33

Title

Association of tumor development with increased cellular proliferation and transgene overexpression, but not c-Ha-ras mutations, in v-Ha-ras transgenic Tg.AC mice.

Authors

Hansen LA; Trempus CS; Mahler JF; Tennant RW

Journal

Carcinogenesis

Volume

17

Issue

9

Year

1996

Pages

1825-33

Abstract

The transgenic mouse line Tg.AC carries a v-Ha-ras gene fused to a fetal (zeta) globin promoter and uniquely responds to chemical carcinogens and tumor promoters by the induction of epidermal papillomas. Although the transgene was not constitutively expressed in non-tumor-bearing tissues, expression was induced by exposure to selected chemicals. Tg.AC transgenic mice on the FVB/N background developed occasional spontaneous tumors, including odontomas, squamous cell carcinoma of the salivary gland, leukemias and a rare ovarian yolk sac carcinoma. Both spontaneous and induced tumors are associated with expression of the transgene and, as determined by in situ hybridization, transgene expression is localized to proliferative areas of the tumors. Sequence analysis of the endogenous c-Ha-ras gene in both induced and spontaneous tumors revealed no mutations in codons 12, 59 or 61. These results suggest that expression of the v-Ha-ras transgene induces proliferation of specific cells in diverse tissues which then acquire neoplastic properties.

Links

J:55156 – Mouse Genome Informatics
8824502 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Leukocyte leukemia Leukocyte

observed

FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Salivary gland squamous cell carcinoma Salivary gland

observed

FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
Skin - Dorsal region

very high

FVB/NTac Skin papilloma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
  • dimethylbenzanthracene (DMBA)
Skin - Dorsal region

observed

FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin squamous cell carcinoma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
Skin - Dorsal region

observed

FVB/NTac Skin squamous cell carcinoma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
  • dimethylbenzanthracene (DMBA)
Skin - Dorsal region

observed

FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma Tooth

observed

FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Yolk sac carcinoma Yolk sac

sporadic

FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed (Unspecified organ) tumor - spindle cell
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
Skin - Dorsal region

observed