Project description:A Stat3-dependent transcription regulatory network involved in inflammation and metastasis is identified. Analyses of the gene expression data revealed that Stat3flx/flx/NIC tumors exhibited a significant reduction in the expression of factors involved in both tumor angiogenesis (fibronectin, von willebrand factor, annexin a3, thrombopoietin, fibulin 5) and in the acute phase inflammatory response (cebpd, osmr, saa1, saa2) Experiment Overall Design: Common reference design. 8 samples including RNA extracted from 3 pools of Stat3wt/wt/NIC (WT) tumor tissues (5 individual tumor samples per pool) and 5 individual Stat3flx/flx/NIC (Homo) tumor tissue samples.
Project description:Overexpression and/or amplification of the ErbB-2 oncogene, as well as inactivation of the tumor suppressor PTEN, are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the MMTV promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (MMTV-NIC). Disruption of PTEN in the mammary epithelium of the MMTV-NIC model system dramatically accelerated the formation of multifocal and highly metastatic mammary tumors, which exhibit homogenous pathology. PTEN-deficient/NIC tumorigenesis was associated with an increase in angiogenesis. Moreover, inactivation of PTEN in the MMTV-NIC mouse model resulted in hyperactivation of the PI3K/Akt signalling pathway. However, like the parental strain, tumors obtained from PTEN-deficient/NIC mice displayed histopathological and molecular features of the luminal-like subtype of breast cancer. Taken together, our findings provide important implications in understanding the molecular determinants of mammary tumorigenesis driven by PTEN deficiency and ErbB-2 activation, and could provide a valuable tool for testing the efficacy of therapeutic strategies that target these critical signalling pathways.
Project description:Overexpression and/or amplification of the ErbB-2 oncogene, as well as inactivation of the tumor suppressor PTEN, are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the MMTV promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (MMTV-NIC). Disruption of PTEN in the mammary epithelium of the MMTV-NIC model system dramatically accelerated the formation of multifocal and highly metastatic mammary tumors, which exhibit homogenous pathology. PTEN-deficient/NIC tumorigenesis was associated with an increase in angiogenesis. Moreover, inactivation of PTEN in the MMTV-NIC mouse model resulted in hyperactivation of the PI3K/Akt signalling pathway. However, like the parental strain, tumors obtained from PTEN-deficient/NIC mice displayed histopathological and molecular features of the luminal-like subtype of breast cancer. Taken together, our findings provide important implications in understanding the molecular determinants of mammary tumorigenesis driven by PTEN deficiency and ErbB-2 activation, and could provide a valuable tool for testing the efficacy of therapeutic strategies that target these critical signalling pathways. Experiment Overall Design: Common reference design. 9 samples (including 2 normal tissue and 7 tumor tissue samples) replicated twice as dye swaps, generating a total of 18 arrays.
Project description:A Stat3-dependent transcription regulatory network involved in inflammation and metastasis is identified. Analyses of the gene expression data revealed that Stat3flx/flx/NIC tumors exhibited a significant reduction in the expression of factors involved in both tumor angiogenesis (fibronectin, von willebrand factor, annexin a3, thrombopoietin, fibulin 5) and in the acute phase inflammatory response (cebpd, osmr, saa1, saa2)
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
