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  • Title: Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas.
    Author: Theodorou V, Boer M, Weigelt B, Jonkers J, van der Valk M, Hilkens J.
    Journal: Oncogene; 2004 Aug 12; 23(36):6047-55. PubMed ID: 15208658.
    Abstract:
    Mouse mammary tumor virus (MMTV) infection causes a high incidence of murine mammary carcinomas by insertion of its proviral DNA in the genome of mammary epithelial cells. Retroviral insertion can activate flanking proto-oncogenes by a process called insertional mutagenesis. By sequencing the DNA adjacent to MMTV proviral insertions in mammary tumors from BALB/c mice infected with C3H-MMTV, we have found a common MMTV insertion site in the Fgf10 locus. RT-PCR studies showed that Fgf10 is expressed only in those tumors harboring a MMTV proviral insertion in this locus, suggesting that Fgf10 is a proto-oncogene. The oncogenicity of Fgf10 was evaluated in vivo by subcutaneous transplantation of retrovirally transduced HC11 mammary epithelial cells into BALB/c mice. Highly vascularized invasive subcutaneous tumors developed indicating that Fgf10 can act as an oncogene. A survey of primary human breast carcinomas revealed strongly elevated Fgf10 mRNA levels in approximately 10% of the tumors tested, suggesting that Fgf10 may also be involved in oncogenicity of a subset of human breast cancers.
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