Project description:This SuperSeries is composed of the following subset Series: GSE30864: Gene expression of polyoma middle T antigen induced mammary tumors [AKXD x PyMT] GSE30865: Gene expression of polyoma middle T antigen induced mammary tumors [NZB x PyMT] GSE31223: Gene expression of polyoma middle T antigen induced mammary tumors [RNA_Seq : MOLF x PyMT] Refer to individual Series
Project description:Conventional transgenic and knockout models do not allow selective introduction of oncogenic alterations into the progenitor population of mammary cells; thus, the role of progenitor cells in mammary tumorigenesis is yet unknown. By generating transgenic mice expressing tva – encoding the receptor for avian leukosis virus subgroup A (ALV/A) – from the Keratin 6a (K6) gene promoter, we found that K6+ mammary cells are bipotential progenitor cells, but not stem cells. These K6+ cells were readily induced to form tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding polyoma middle T antigen. Compared with tumors induced by the same oncogene-expressing virus in transgenic mice expressing tva from the commonly used MMTV LTR or other murine models of breast cancer, tumors in this K6-tva line were unique in that they resemble the normal breast-like subtype of human breast cancer. Consequently, these observations suggest that the cell of origin affects mammary tumor phenotypes. This K6-tva model may be useful for preclinical testing of targeted therapy for normal-like breast cancers in patients. Keywords: Three group comparison We carried out Affymetrix array analysis of five RCAS-PyMT-induced tumors each from K6-tva mice and MMTV-tva mice, as well as five mammary tumors from MMTV-PyMT transgenic mice.
Project description:The aim of this investigation was to study the consequences of interfering with soluble epoxide hydrolase (sEH) expression on tumor growth and metastasis in genetically modified animals that spontaneously generate tumors without the exogenous application of high concentrations of epoxide mediators or inhibitors. Therefore, breast cancer development was studied in mice expressing the polyoma middle T oncogene (PyMT) under the control of the mouse mammary tumor virus promoter, to induce spontaneous mammary tumors. To facilitate the study of endogenous sEH activity in tumor growth, PyMT mice were then crossed with sEH-/- mice to generate sEH-deficient mice that spontaneously generate breast tumors (so called PyMTsEH mice). For these analyses, primary tumors were removed from 20 week old mice.
Project description:Conventional transgenic and knockout models do not allow selective introduction of oncogenic alterations into the progenitor population of mammary cells; thus, the role of progenitor cells in mammary tumorigenesis is yet unknown. By generating transgenic mice expressing tva – encoding the receptor for avian leukosis virus subgroup A (ALV/A) – from the Keratin 6a (K6) gene promoter, we found that K6+ mammary cells are bipotential progenitor cells, but not stem cells. These K6+ cells were readily induced to form tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding polyoma middle T antigen. Compared with tumors induced by the same oncogene-expressing virus in transgenic mice expressing tva from the commonly used MMTV LTR or other murine models of breast cancer, tumors in this K6-tva line were unique in that they resemble the normal breast-like subtype of human breast cancer. Consequently, these observations suggest that the cell of origin affects mammary tumor phenotypes. This K6-tva model may be useful for preclinical testing of targeted therapy for normal-like breast cancers in patients. Keywords: Three group comparison
Project description:Breast cancer is a multifaceted disease, exhibiting significant molecular, histological, and pathological diversity. Factors that impact this heterogeneity are poorly understood; however, transformation of distinct normal cell populations of the breast may generate different tumor phenotypes. Our previous study demonstrates that the polyomavirus middle T antigen (PyMT) oncogene can establish diverse tumor subtypes when broadly expressed within mouse mammary epithelial cells. Herein, we assess the molecular, histological, and metastatic outcomes from distinct mammary cell populations transformed with PyMT. By combining several methodologies, including lentiviral infection, cell sorting, and transplantation, we have characterized tumors arising from enriched populations of mammary epithelial cells. We have found that expression of PyMT within different cell populations influences tumor histology, molecular subtype, and metastatic potential. 32 samples, 1 from each of 32 mouse mammary tumors arising from transplanted mouse mamary epithelial cells (MMECs) transduced with PyMT-expressing lentivirus. MMECs were sorted into four different types prior to transplant: luminal CD133+ (8 samples), luminal CD133- (11 samples), stem (6 samples), and basal (7 samples). The background for the cell donor and transplant recipients mice was FVB/NJ obtained from Jackson Laboratories.
Project description:Breast carcinoma cell invasion is thought to depend on the mobilization of the membrane-anchored matrix metalloproteinase, Mmp14/MT1-MMP, to drive the remodeling of extracellular matrix and trigger associated signaling cascades. However, the roles that this proteinase plays during breast tumor progression and invasion in vivo remain undefined. A highly penetrant syngeneic mouse model for luminal B breast cancer driven by the polyoma middle T (PyMT) antigen, in tandem with recently developed Mmp14-floxed mice and MMTV-Cre transgenics that express Cre recombinase throughout the mammary epithelial cell compartment, were used to characterize the impact of conditional Mmp14-targeting on breast carcinoma cell invasion programs in vivo. Transcriptome profiling of intact MMTV-PyMT carcinoma tumors was used to investigate the functional roles of carcinoma cell-derived MT1-MMP in MMTV-PyMT tumor progression and invasion in an unbiased fashion
Project description:Breast cancer is a multifaceted disease, exhibiting significant molecular, histological, and pathological diversity. Factors that impact this heterogeneity are poorly understood; however, transformation of distinct normal cell populations of the breast may generate different tumor phenotypes. Our previous study demonstrates that the polyomavirus middle T antigen (PyMT) oncogene can establish diverse tumor subtypes when broadly expressed within mouse mammary epithelial cells. Herein, we assess the molecular, histological, and metastatic outcomes from distinct mammary cell populations transformed with PyMT. By combining several methodologies, including lentiviral infection, cell sorting, and transplantation, we have characterized tumors arising from enriched populations of mammary epithelial cells. We have found that expression of PyMT within different cell populations influences tumor histology, molecular subtype, and metastatic potential.
Project description:We report the small RNA sequencing results of mouse pancreatic tumor cell lines driven by polyoma middle-T antigen, which have additionally been engineered to have either wild-type (herein "PDwt") or single-copy loss (herein "PDhet") of the Dicer gene. As expected, PDhet cell lines exhibit lower miRNA levels compared to PDwt cell lines. Principle component analysis, detailed in the published manuscript, reveals PDwt cell lines to be more widely varying in miRNA signature compared to PDhet cell lines. Grouping miRNAs by family reveals several families to be significantly downregulated in PDhet cells lines below 50% of PDwt levels, including miR-10, -148, -17, -28, -299, -30, -34, and -379.