Reference SummaryMuller WJ, Cell 1988 Jul 1;54(1):105-15

Title

 Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene.

Authors

 Muller WJ; Sinn E; Pattengale PK; Wallace R; Leder P

Journal

 Cell

Volume

 54

Issue

 1

Year

 1988

Pages

 105-15

Abstract

 We have used transgenic mice that carry an activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV) promoter to assess the stepwise progression of carcinogenesis in mammary epithelium. Unlike the stochastic occurrence of solitary mammary tumors in transgenic mice bearing the MMTV/c-myc or the MMTV/v-Ha-ras oncogenes, transgenic mice uniformly expressing the MMTV/c-neu gene develop mammary adenocarcinomas that involve the entire epithelium in each gland. Because these tumors arise synchronously and are polyclonal in origin, expression of the activated c-neu oncogene appears to be sufficient to induce malignant transformation in this tissue in a single step. In contrast, expression of the c-neu transgene in the parotid gland or epididymis leads to benign, bilateral epithelial hypertrophy and hyperplasia which does not progress to full malignant transformation during the observation period. These results indicate that the combination of activated oncogene and tissue context are major determinants of malignant progression and that expression of the activated form of c-neu in the mammary epithelium has particularly deleterious consequences.

Links

 J:48632 – MGI References
2898299 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/N-Tg(MMTV-Erbb2)NA1Mul High levels of transgene expression were detected in salivary gland, epididymis, and at lower levels detected in Harderian gland. Transgene expression was not detected in the liver.
Hyperplasia of the epididymis was associated with low fertility in this mouse.
FVB/N-Tg(MMTV-Erbb2)NB1Mul High levels of transgene expression were detected in the epididymis and Harderian gland. Transgene expression was not detected in the liver or in the salivary gland.
Hyperplasia of the epididymis was associated with low fertility in this mouse.
FVB/N-Tg(MMTV-Erbb2)NF1Mul Female mice have a lactation defect and are unable to nurse their young.
High levels of transgene expression were detected in mammary gland, and lower levels were detected in salivary gland and lung. Transgene expression was not detected in the liver or in the Harderian gland.
High levels of transgene expression were detected in mammary gland and salivary gland, and lower levels were detected in epididymis and Harderian gland. Transgene expression was not detected in the liver.
Hyperplasia of the epididymis was associated with low fertility in these mice. Only 2 of 12 had sired litters (only 1 litter each).
Male mice displayed low fertility and had difficulty siring litters.
FVB/N-Tg(MMTV-Erbb2)NK1Mul Expression of transgene was not detected in salivary gland, Harderian gland or liver. Expression of transgene was also not detected in normal virgin mammary glands.
FVB/N-Tg(MMTV-Erbb2)NL1Mul Expression of the transgene was not detected in mammary tumors, salivary gland, Harderian gland, or liver.
FVB/N-Tg(MMTV-Erbb2)NM1Mul Expression of the transgene was not detected in mammary tumors, salivary gland, Harderian gland, or liver.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(MMTV-Erbb2)NA1Mul Epididymis hyperplasia - papillary Epididymis

100
FVB/N-Tg(MMTV-Erbb2)NB1Mul Epididymis hyperplasia - papillary Epididymis

100
FVB/N-Tg(MMTV-Erbb2)NF1Mul Epididymis hyperplasia - papillary Epididymis

very high
FVB/N-Tg(MMTV-Erbb2)NF1Mul Epididymis tumor Epididymis

0
FVB/N-Tg(MMTV-Erbb2)NA1Mul Eye - Harderian gland lesion Eye - Harderian gland

0
FVB/N-Tg(MMTV-Erbb2)NB1Mul Eye - Harderian gland lesion Eye - Harderian gland

0
FVB/N-Tg(MMTV-Erbb2)NF1Mul Eye - Harderian gland lesion Eye - Harderian gland

0
FVB/N-Tg(MMTV-Erbb2)NA1Mul Mammary gland adenocarcinoma Mammary gland

100
FVB/N-Tg(MMTV-Erbb2)NF1Mul Mammary gland adenocarcinoma Mammary gland

100
FVB/N-Tg(MMTV-Erbb2)NK1Mul Mammary gland adenocarcinoma Mammary gland

observed
FVB/N-Tg(MMTV-Erbb2)NL1Mul Mammary gland adenocarcinoma Mammary gland

observed
FVB/N-Tg(MMTV-Erbb2)NM1Mul Mammary gland adenocarcinoma Mammary gland

observed
FVB/N-Tg(MMTV-Erbb2)NF1Mul Mammary gland dysplasia Mammary gland

very high
FVB/N-Tg(MMTV-Erbb2)NF1Mul Mammary gland hyperplasia Mammary gland

very high
FVB/N-Tg(MMTV-Erbb2)NF1Mul Salivary gland - Parotid dysplasia Salivary gland - Parotid

100
FVB/N-Tg(MMTV-Erbb2)NA1Mul Salivary gland - Parotid hyperplasia Salivary gland - Parotid

100
FVB/N-Tg(MMTV-Erbb2)NF1Mul Salivary gland - Parotid hyperplasia Salivary gland - Parotid

0 - 100
FVB/N-Tg(MMTV-Erbb2)NF1Mul Salivary gland - Parotid tumor Salivary gland - Parotid

0