Project description: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.
Project description:To characterise the metabolic landscape of metastatic breast cancer we investigated differences in metabolites between the serum of MMTV-PyMT (Mouse Mammary Tumor Virus long terminal repeat upstream of a cDNA sequence encoding the Polyoma Virus middle T antigen) mice and their wild-type counterparts (https://doi.org/10.1101/2024.07.02.601676). Here we provide matched transcriptomic data on the primary mammary tumors from MMTV-PyMT mice and the mammary gland from FVB/N mice
Project description:Junction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature. Each 3 MMTV-PyMT JAm-A+/+ (JamA+) and 3 MMTV JAM-A-/- (JamA-) mammary tumor were resected at early stages of tumor development for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Junction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature.
