AI Article Synopsis
- MMTV infection leads to a high rate (90-95%) of mammary tumors in genetically susceptible mice by causing mutations through insertion into their DNA, influenced by steroid hormones.
- Researchers conducted expression profiling to identify the active proto-oncogenes associated with MMTV insertions in tumors, using real-time quantitative RT-PCR to validate results.
- The study suggests that specific MMTV insertions trigger a series of biological changes, establishing a distinct molecular signature characteristic of the tumors induced by these viruses.
Article Abstract
Exogenous infection by milk-borne mouse mammary tumor viruses (MMTV) typically induce mouse mammary tumors in genetically susceptible mice at a rate of 90-95% by 1 year of age. In contrast to other transforming retroviruses, MMTV acts as an insertional mutagen and under the influence of steroid hormones induces oncogenic transformation after insertion into the host genome. As these events correspond with increases in adjacent proto-oncogene transcription, we used expression array profiling to determine which commonly associated MMTV insertion site proto-oncogenes were transcriptionally active in MMTV induced mouse mammary tumors. To verify our gene expression array results we developed real-time quantitative RT-PCR assays for the common MMTV insertion site genes found in RIII/Sa mice (int-1/wnt-1, int-2/fgf-3, int-3/Notch 4, and fgf8/AIGF) as well as two genes that were consistently up regulated (CCND1, and MAT-8) and two genes that were consistently down regulated (FN1 and MAT-8) in the MMTV induced tumors as compared to normal mammary gland. Finally, each tumor was also examined histopathologically. Our expression array findings support a model whereby just one or a few common MMTV insertions into the host genome sets up a dominant cascade of events that leave a characteristic molecular signature.
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| http://dx.doi.org/10.1016/j.virusres.2006.01.006 | DOI Listing |
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