Gene expression array analyses predict increased proto-oncogene expression in MMTV induced mammary tumors

Area of Science:

• Oncology
• Virology
• Genetics

Background:

• Milk-borne mouse mammary tumor viruses (MMTV) induce tumors in susceptible mice (90-95% by 1 year).
• MMTV acts as an insertional mutagen, driving oncogenic transformation via steroid hormone influence after host genome insertion.
• Insertions correlate with increased adjacent proto-oncogene transcription.

Purpose of the Study:

• To identify transcriptionally active proto-oncogenes at common MMTV insertion sites in MMTV-induced mouse mammary tumors.
• To validate gene expression array findings using real-time quantitative RT-PCR.

Main Methods:

• Expression array profiling to assess proto-oncogene transcription in MMTV-induced tumors.
• Real-time quantitative RT-PCR assays to verify expression levels of MMTV insertion site genes (int-1/wnt-1, int-2/fgf-3, int-3/Notch 4, fgf8/AIGF), upregulated genes (CCND1, MAT-8), and downregulated genes (FN1, MAT-8).
• Histopathological examination of tumors.

Main Results:

• Expression array profiling identified transcriptionally active proto-oncogenes at common MMTV insertion sites.
• RT-PCR confirmed differential expression of specific genes, including upregulation of CCND1 and MAT-8, and downregulation of FN1 and MAT-8 in MMTV-induced tumors compared to normal mammary glands.
• Findings support a model where limited MMTV insertions initiate a cascade of molecular events.

Conclusions:

• MMTV insertions trigger a dominant cascade of gene expression changes.
• These alterations create a characteristic molecular signature in MMTV-induced mouse mammary tumors.
• Understanding these molecular events aids in comprehending MMTV-driven oncogenesis.