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Publication : A single nucleotide change in the mouse genome accelerates breast cancer progression.

First Author  Seitzer N Year  2010
Journal  Cancer Res Volume  70
Issue  2 Pages  802-12
PubMed ID  20068154 Mgi Jnum  J:156750
Mgi Id  MGI:4421326 Doi  10.1158/0008-5472.CAN-09-3239
Citation  Seitzer N, et al. (2010) A single nucleotide change in the mouse genome accelerates breast cancer progression. Cancer Res 70(2):802-12
abstractText  In the growth factor receptor gene FGFR4 the presence of the common single nucleotide polymorphism Arg388 has been associated with progression of various types of cancer including breast cancer. However, a causative relationship is not readily assigned due to genetic heterogeneity in different patient cohorts. To address this issue, we compared the effects of this allele on malignant progression in the WAP-TGFalpha transgenic mouse model of breast cancer. A knock-in strain was generated to introduce an analogous Arg385 allele into the murine FGFR4 gene. Mouse embryonic fibroblasts derived from this strain displayed accelerated cell transformation, with transformed cells exhibiting greater motility and invasive behavior. In the in vivo context of TGFalpha-induced mammary carcinogenesis, tumor development and progression was significantly advanced in tumor mass, size, and onset of pulmonary metastases. Our findings definitively identify the FGFR4 Arg388 allele as a functional prognostic marker for breast cancer progression.
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