Late Developing Mammary Tumors and Hyperplasia Induced by a Low-Oncogenic Variant of Mouse Mammary Tumor Virus (MMTV) Express Genes Identical to Those Induced by Canonical MMTV

Background: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes. Findings: We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3. Conclusions: These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant