Gene expression profiling of advanced murine K-RasG12V lung adenocarcinomas
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ABSTRACT: We aimed to analyze the transcriptional profile of full-blown murine lung adenocarcinomas driven by K-RasG12V oncogene. We used a GEM model of lung adenocarcinoma driven by a resident K-RasG12V oncogene. On average, tumors were collected 10 months after Adeno-CRE infection.
Project description:We aimed to analyze the transcriptional profile of lung epithelial cells early after the expression of a resident K-RasG12V oncogene. This approach was based on the rationale that valuable therapeutic targets should be easier to detect in the first stages of tumor development due to tumor heterogeneity which occurr at late stages. We used a GEM model of lung adenocarcinoma driven by a resident K-RasG12V oncogene. In this GEM, the K-RasG12V allele also expresses a color marker that allows identification of K-RasG12V expressing cells at the single cell level in tissue sections. Thanks to this strategy we isolated early K-RasG12V-driven hyperplastic lesions (about 500 cells) and analyzed their gene expression profiling by Affymetrix GeneChip hybridization. Normal cells were isolated accordingly by LCM in the same lung sections.
Project description:microarray analysis with and without sh-p53 in IMR90 (normal human diploid fiborblasts) Phenotypes were created by overexpression of RasG12V, E1A/RasG12V in IMR90 cells, in growing IMR90, inr quiescent IMR90 cells (3 days confluence) and 24 or 48 hours Etoposide treated IMR90 cells were subjected to lentiviral knockdown of p53 or vector
Project description:p53 ChIP seq and Histone mark ChIP Seq data in IMR90 (normal human diploid fibroblasts) Phenotypes were created by overexpression of RasG12V, E1A/RasG12V in IMR90 cells, growing IMR90 and 24 hour Etoposide treated IMR90 cells were subjected to p53 and histone mark ChIP Seq
Project description:In the developing heart, heterotypic transcription factors (TFs) interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5 have been proposed as a mechanism for human congenital heart disease. In order to study the role of each TF during heart formation, embryonic stem (ES) cell-derived embryos were generated from KO ES cells for Tbx5, Nkx2-5 or both TFs. We used microarrays to identify changes in the gene expression due to the lack of Tbx5, Nkx2-5 or both TFs during early heart formation. WT, Nkx2-5KO (NKO), Tbx5KO (TKO) and Tbx5KO;Nkx2-5KO (DKO) E8.75 mouse hearts were microdissected for RNA extraction and hybridization on Affymetrix microarrays.
Project description:We aimed to analyze the transcriptional profile of lung epithelial cells early after the expression of a resident K-RasG12V oncogene. This approach was based on the rationale that valuable therapeutic targets should be easier to detect in the first stages of tumor development due to tumor heterogeneity which occurr at late stages.
Project description:We report that the cell of origin plays an important role in this metastatic tropism. Following injection into the arterial circulation of mice, each of the identically transformed cell types gave rise to different metastatic patterns. Using gene expression analysis, we identified the chemokine receptor CXCR4 as being instrumental in determining the distinct metastatic patterns between skeletal muscle precursor cells and skeletal myoblasts. 3 independent cell lines of primary human skeletal myoblasts, primary skeletal muscle cell precursors, and each of these cell lines transformed with hTERT, the early region of SV40 encoding T-Ag and t-Ag, and RasG12V analysis of primary human skeletal myoblasts, primary skeletal muscle cell precursors, and each of these cell lines transformed with hTERT, the early region of SV40 encoding T-Ag and t-Ag, and RasG12V
Project description:Our mechanistic studies shed light on the central role of the proto-oncogene MYC in driving global protein anabolism and the ER stress response. Specifically, the MYC-p19ARF-TP53 axis plays a critical role in regulating proteostasis and an increased demand for protein disposal.