Reference SummaryKitsberg DI, Oncogene 1996 Dec 19;13(12):2507-15

Title

 Keratinocyte growth factor induces mammary and prostatic hyperplasia and mammary adenocarcinoma in transgenic mice.

Authors

 Kitsberg DI; Leder P

Journal

 Oncogene

Volume

 13

Issue

 12

Year

 1996

Pages

 2507-15

Abstract

 The kinetics of solitary mammary tumor formation in transgenic mice bearing the MMTV-int-2 (fgf3) fusion gene suggest that several genetic events are required for tumorigenesis. In an effort to identify elements that could contribute to this oncogenic process, we used differential display PCR to identify gene products that are strongly and specifically induced in int-2 mammary tumors. Using this approach we identified a member of the FGF family, kgf (fgf7), as a gene that is strongly upregulated in an int-2-containing mammary tumor. Since int-2 and kgf strongly bind the same receptor, the IIIb isoform of FGFR2, it is possible that their joint expression, one as a transgene, the other as an activated gene, might reinforce the same mitogenic pathway. To test this possibility, we created transgenic mice that carry kgf as a transgene gene under the control of the MMTV promoter/enhancer. Female mice carrying this transgene develop a very dramatic mammary epithelial hyperplasia and go on to develop solitary, metastatic adenocarcinomas of the mammary gland. Consistent with a common signalling pathway, the MMTV-kgf-induced hyperplasia has the morphologic characteristics of that seen in the MMTV-int-2 mice. Male mice also develop hyperplasia of the male genital tract, including the seminal vesicle, the vas deferens and the prostate. Thus KGF can act as a potent proliferative inducer in mammary and specific urogenital tissue and can contribute to the development of adenocarcinoma of the mammary gland in a manner strongly reminiscent of receptor-related ligand, int-2.

Links

 J:37679 – MGI References
9000125 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/N-Tg(MMTV-Fgf7)1Led Females of this strain cannot nurse their young.
Males "have severe difficulty in fertilizing females. Most are incapable of doing so and those that succeed can do so only shortly after puberty with the sterility phenotype increasing with age."

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(MMTV-Fgf7)1Led Mammary gland adenocarcinoma Mammary gland

observed
FVB/N-Tg(MMTV-Fgf7)1Led Mammary gland hyperplasia Mammary gland

100
FVB/N-Tg(MMTV-Fgf7)1Led Mammary gland keratoacanthoma Mammary gland

observed
FVB/N-Tg(MMTV-Fgf7)1Led Mammary gland tumor Mammary gland

93
FVB/N-Tg(MMTV-Fgf7)1Led Mesodermal cell/mesoblast sarcoma Mammary gland

observed
FVB/N-Tg(MMTV-Fgf7)1Led Prostate gland - Dorsolateral lobe dysplasia Prostate gland - Dorsolateral lobe

observed
FVB/N-Tg(MMTV-Fgf7)1Led Prostate gland - Dorsolateral lobe hyperplasia - papillary Prostate gland - Dorsolateral lobe

100
FVB/N-Tg(MMTV-Fgf7)1Led Prostate gland - Ventral lobe dysplasia Prostate gland - Ventral lobe

observed
FVB/N-Tg(MMTV-Fgf7)1Led Prostate gland - Ventral lobe hyperplasia - papillary Prostate gland - Ventral lobe

100
FVB/N-Tg(MMTV-Fgf7)1Led Seminal vesicle hyperplasia Seminal vesicle

observed
FVB/N-Tg(MMTV-Fgf7)1Led Vas deferens hyperplasia - papillary Vas deferens

observed