MMTV-Fgf8 transgenic mice develop mammary and salivary gland neoplasia and ovarian stromal hyperplasia
| Autor: | Craig A. MacArthur, Gregory M. Shackleford, Avril Lawshé, D B Shankar, D Daphna-Iken, David M. Ornitz |
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| Rok vydání: | 1998 |
| Předmět: |
Genetically modified mouse
Male Cancer Research medicine.medical_specialty animal structures Fibroblast Growth Factor 8 Transgene Virus Integration Mammary gland Mice Transgenic Adenocarcinoma medicine.disease_cause Neoplasms Multiple Primary Mice stomatognathic system Internal medicine Genetics medicine Animals Northern blot Transgenes Neoplasm Metastasis Promoter Regions Genetic Molecular Biology Hyperplasia biology Salivary gland Mouse mammary tumor virus Ovary Mammary Neoplasms Experimental Ovarian Stromal Hyperplasia biology.organism_classification Salivary Gland Neoplasms Fibroblast Growth Factors Mice Inbred C57BL Carcinoma Lobular medicine.anatomical_structure Endocrinology Gene Expression Regulation Mammary Tumor Virus Mouse Cancer research Female Stromal Cells Carcinogenesis |
| Zdroj: | Oncogene. 17(21) |
| ISSN: | 0950-9232 |
| Popis: | Prior studies have identified Fibroblast Growth Factor-8 (Fgf8) as a possible proto-oncogene in mouse mammary tumorigenesis. We now report on the generation of two types of Fgf8 transgenic mice that each utilize the mouse mammary tumor virus (MMTV) promoter. The first transgene (MMTV-Fgf8b) results in the overexpression of the FGF8b isoform exclusively. Male and female MMTV-Fgf8b transgenic mice are viable and fertile. RNA for FGF8b is detected in mammary gland and salivary gland tissues of transgenic mice by Northern blot analysis. Nearly 85% of breeding transgenic female mice developed mammary lobular adenocarcinomas by 12 months of age, while no tumors developed in non-transgenic littermates. Salivary gland tumors occurred in some animals, always in association with mammary tumors. Several MMTV-Fgf8b transgenic mice had lung metastases at necropsy. The second transgene (MMTV-Fgf8) uses the entire Fgf8 gene and potentially encodes all FGF8 isoforms. Fgf8 is expressed by this transgene in several tissues in addition to those described above, notably the ovaries. The two MMTV-Fgf8 founders developed mammary ductal adenocarcinomas at five and eight months of age, and both displayed ovarian stromal hyperplasia. The founders expressing either transgene did not successfully nurse their pups. These results demonstrate that production of FGF8b, and possibly other FGF8 isoforms, in the mammary and salivary glands contributes to oncogenesis, and that ovarian expression results in stromal hyperplasia. |
| Databáze: | OpenAIRE |
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