Project description:Comparative analysis of the transcriptome of primary tumors generated from 4T1 cells transduced with a lentiviral vector expressing a siRNA against murine SPARC (4T1-C18), primary tumors generated from 4T1 cells transduced with a lentiviral vector expressing a scramble sequence (4T1-SCR) or lung metastasis foci from 4T1-SCR tumor-bearing mice (4T1-SCR MTTS). Three experimental conditions, 4T1-C18, 4T1-SCR and 4T1-SCR MTTS. Biological replicates: 4 4T1-C18, 4 4T1-SCR, 4 4T1-SCR MTTS independently grown in different mice. 2 days-old tumors and 30 days old lung foci. One replicate per array. All microarrays were processed the same day
Project description:Comparative analysis of the transcriptome of primary tumors generated from 4T1 cells transduced with a lentiviral vector expressing a siRNA against murine SPARC (4T1-C18), primary tumors generated from 4T1 cells transduced with a lentiviral vector expressing a scramble sequence (4T1-SCR) or lung metastasis foci from 4T1-SCR tumor-bearing mice (4T1-SCR MTTS).
Project description:Comparative analysis of the transcriptome of 4T1 cells stably transduced with a lentiviral vector expressing a siRNA against murine SPARC (4T1-C18) with 4T1 control cells stably transduced with a lentiviral vector expressing a scramble sequence (4T1-SCR). Two-condition experiment, 4T1-C18 vs. 4T1-SCR cells. Biological replicates: 4 SPARC knock down, 4 control, independently grown in vitro and harvested. One replicate per array. Microarrays were hybridized in three different days.
Project description:We recently established an orthotopic breast cancer model of brain metastasis based on the injection of murine breast cancer cell lines into the mammary fat pad. This model is based on the use of 4T1 murine breast carcinoma cells. 4T1-derived tumors recapitulate the main steps of human breast cancer progression, including epithelial-to-mesenchymal transition and metastases to lung and lymph nodes. Bioluminescence imaging revealed the appearance of secondary lesions to the lung and lymph nodes and sporadically to the brain. Brain metastases were confirmed by macroscopic and microscopic evaluation of the brains at necropsy. We then isolated brain metastatic cells, re-injected them orthotopically in syngeneic (BALB/c) mice and isolated again cell lines from brain metastatic lesions for two rounds of selection. We obtained a cell line metastasizing to the brain with 100% penetrance (named 4T1-BM2 for Brain Metastasis, 2nd generation). In parallel we derived after two rounds of in vivo growth tumor cell lines from primary tumors (4T1-T2) and from lung metastases (4T1-LM2).
Project description:Comparative analysis of the transcriptome of 4T1 cells stably transduced with a lentiviral vector expressing a siRNA against murine SPARC (4T1-C18) with 4T1 control cells stably transduced with a lentiviral vector expressing a scramble sequence (4T1-SCR).
Project description:The immune signaling protein NLRX1 can be either tumor promoting or tumor suppressing in different models of cancer. We demonstrate that in a mammary tumor model of triple-negative breast cancer, NLRX1 impacts tumor volume and lung metastasis. We used this microarray to understand what genes and pathways are impacted by NLRX1 in murine triple-negative mammary tumors to produce the in vivo phenotypes we observed. Abstract from associated publication: Prior studies have defined multiple, but inconsistent, roles for NLRX1 in regulating cancer-associated biological functions. Here, we explore the role of NLRX1 in the highly-metastatic murine 4T1 mammary tumor model. Using Nlrx1-/- mice engrafted with 4T1 tumors, we demonstrate that NLRX1 functions as a tumor suppressor when expressed in healthy host cells. Specifically, NLRX1 attenuates tumor growth and metastasis through suppressing epithelial-mesenchymal transition, tumor-associated eosinophil recruitment, and the lung metastatic niche. Conversely, we demonstrate that NLRX1 functions as a tumor promoter when expressed in 4T1 tumor cells using gain- and loss-of-function studies. Mechanistically, NLRX1 augments 4T1 aggressiveness through regulating epithelial-mesenchymal transition, cell death, proliferation, migration, ROS levels, and mitochondrial respiration. Together, we provide critical insight into NLRX1 function in breast cancer and establish cellular context as the director of the dichotomous role of NLRX1 in mammary tumor metastasis.