Reference SummaryNielsen LL, Cancer Res 1992 Jul 1;52(13):3733-8

Title

Evaluation of the wap-ras transgenic mouse as a model system for testing anticancer drugs.

Authors

Nielsen LL; Gurnani M; Tyler RD

Journal

Cancer Res

Volume

52

Issue

13

Year

1992

Pages

3733-8

Abstract

Transgenic mouse models have provided many valuable insights into the molecular mechanisms of tumorigenesis; unfortunately, there is a paucity of published information on the utility of these models for evaluating potential anticancer therapeutics. Line 69 wap-ras transgenic mice have an activated, human c-Ha-ras gene on their Y chromosome. Adult males develop salivary and/or mammary adenocarcinomas. Both tumor types express high levels of human ras oncoprotein. Two new sublines, designated wap-ras/F, were created by selective breeding. Subline 69-2 wap-ras/F males developed multiple mammary tumors at puberty. Tumor onset was delayed by cyclophosphamide treatment prior to puberty. Mammary tumors from cyclophosphamide-treated mice weighed 0.57 +/- 0.09 g/mouse (SD +/- SEM; n = 8), while tumors from control mice weighed significantly more at 2.36 +/- 0.25 g/mouse (n = 8; P less than or equal to 0.001; SD +/- SEM). These results suggest that subline 69-2F mice will be valuable for testing therapeutic regimes designed to interfere with processes occurring early in tumorigenesis, before palpable tumor presentation. Tumor sensitivity to several clinically relevant cytotoxins was also tested in adult wap-ras males with palpable tumors. Both salivary and mammary tumors were sensitive to cyclophosphamide and 5-fluorouracil, but not methotrexate. This suggests that wap-ras transgenic mice will indeed be useful in the discovery of novel therapeutics against neoplasia.

Links

J:46461 – MGI References
1617645 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
STOCK Tg(Wap-HRAS)69Lln Chr YSJL Mammary gland carcinoma Mammary gland

100

FVB.B6SJLF1-Tg(Wap-HRAS)69Lln Chr YSJL Mammary gland carcinoma - adenosquamous Mammary gland

100

B6;SJL-Tg(Wap-HRAS)69Lln Chr YSJL Mammary gland carcinoma - adenosquamous Mammary gland

50

B6;SJL-Tg(Wap-HRAS)69Lln Chr YSJL Mammary gland carcinoma - adenosquamous
  • castration
Mammary gland

12

FVB.B6SJLF1-Tg(Wap-HRAS)69Lln Chr YSJL Mammary gland carcinoma - adenosquamous
  • castration
Mammary gland

100

FVB.B6SJLF1-Tg(Wap-HRAS)69-9Lln Chr YSJL Mammary gland tumor Mammary gland

0

B6;SJL-Tg(Wap-HRAS)69Lln Chr YSJL Salivary gland - Submandibular adenocarcinoma Salivary gland - Submandibular

high

B6;SJL-Tg(Wap-HRAS)69Lln Chr YSJL Salivary gland - Submandibular adenocarcinoma
  • castration
Salivary gland - Submandibular

35

FVB.B6SJLF1-Tg(Wap-HRAS)69-9Lln Chr YSJL Salivary gland tumor Salivary gland

0