Small RNA profiling in mouse mammary tumor virus (MMTV) infected cell cultures and induced mammary tumors. Small RNA profiling in mouse mammary tumor virus (MMTV) infected cell cultures and induced mammary tumors

Mouse mammary tumor virus (MMTV) is a complex retrovirus that induces breast cancer in mice in the absence of known virally-encoded oncogenes. Like other non-acute retroviruses, tumorigenesis by MMTV is thought to occur primarily through insertional mutagenesis, leading to the activation of cellular proto-oncogenes and outgrowth of selected cells. In this study, we investigated whether MMTV encodes microRNAs (miRNAs) and/or modulates host miRNAs that could contribute to tumorigenesis. We have applied high throughput small RNA sequencing to the analysis of MMTV-infected cells and MMTV-induced mammary tumors. Our results demonstrate that MMTV does not encode miRNAs. However, MMTV infected cells and MMTV-producing tumors have altered levels of several cellular miRNAs, including increases in the expression of members of the oncogenic miRNA cluster, miR-17-92. Notably, similar changes in levels of these miRNAs have been previously reported in human breast cancers. Combined, our results demonstrate that virally encoded miRNAs do not contribute to MMTV-mediated tumorigenesis, but that changes in specific host miRNAs in infected cells may contribute to virus replication and tumor biology. Overall design: Six samples each, 2 cell lines, 2 glands, and 2 tumors.