Reference SummaryRowse GJ, Cancer Res 1998 Jun 15;58(12):2675-9

Title

 Genetic modulation of neu proto-oncogene-induced mammary tumorigenesis.

Authors

 Rowse GJ; Ritland SR; Gendler SJ

Journal

 Cancer Res

Volume

 58

Issue

 12

Year

 1998

Pages

 2675-9

Abstract

 Modulation of oncogene-induced carcinogenesis by secondary mutation or genetic background may be an important factor in determining the expression of the tumor phenotype. We have investigated the role of loss of function mutations and strain-specific genetic elements in the modulation of oncogene-induced breast cancer using a murine model. FVB female mice transgenic for the rat neu proto-oncogene [mouse mammary tumor virus (MMTV)-neu] developed mammary tumors between 7 and 12 months of age, whereas FVB x C57Bl/6 (F1) MMTV-neu mice had tumor latencies greater than 18 months. The expression level of the neu transgene was equivalent in tumor tissue from both FVB and F1 mice. Furthermore, increased tumor latency did not appear to be associated with a decrease in expression of the neu transgene in the normal mammary gland of F1 mice because immunohistochemical staining for neu expression in the mammary glands of 3-month-old virgin female mice revealed similar levels of protein expression in FVB and F1 animals. When F1 animals were backcrossed one generation onto the FVB strain ([FVB x B6] F1 x FVB), a subset of the resulting offspring developed tumors with a latency equivalent to that of the pure-strain FVB mice. Statistical analysis of the genetic variability in mammary tumor latency indicated that approximately three independent genes were involved in the latency effect. Interestingly, when tumor growth rates were compared in these same animals, F1 mice had significantly faster tumor growth rates compared with FVB mice.

Links

 J:48749 – MGI References
9635596 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6FVBF1-Tg(MMTVneu)202Mul Expression of Erbb2 was detected in mammary glands of virgin mice.
Transgenic males on a FVB/N background were crossed to female C57BL/6 mice to generate these mice.
(C57BL/6 x B6FVBF1)-Tg(MMTVneu)202Mul Transgenic males on a B6FVBF1 genetic background were crossed to female C57BL/6 mice to generate these mice.
FVB/N-Tg(MMTVneu)202Mul Expression of Erbb2 was detected in mammary glands of virgin mice.
Mice were a gift of Dr. W. Muller.
(FVB x B6FVBF1)-Tg(MMTVneu)202Mul Transgenic males on a B6FVBF1 genetic background were crossed to female FVB mice to generate these mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(MMTVneu)202Mul Mammary gland tumor Mammary gland

64
B6FVBF1-Tg(MMTVneu)202Mul Mammary gland tumor Mammary gland

70
(FVB x B6FVBF1)-Tg(MMTVneu)202Mul Mammary gland tumor Mammary gland

75
(C57BL/6 x B6FVBF1)-Tg(MMTVneu)202Mul Mammary gland tumor Mammary gland

0