Project description:The purpose of this study was to assess the preliminary antitumor activity, safety and tolerability of tepotinib in combination with cetuximab in participants with RAS/BRAF wild-type left-sided Metastatic Colorectal Cancer (mCRC) having acquired resistance to anti-epidermal growth factor receptor (EGFR) antibody targeted therapy due to mesenchymal epithelial transition (MET) amplification.
Project description:This SuperSeries is composed of the following subset Series: GSE12811: CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer (expr) GSE12813: CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer (aCGH) Refer to individual Series
Project description:Epithelial-Mesenchymal Transition (EMT) is thought to contribute to cancer metastasis, but its underlying mechanisms are not well understood. To define early steps in this cellular transformation, we analyzed human mammary epithelial cells with tightly regulated expression of Snail-1, a master regulator of EMT. Following Snail-1 induction, epithelial markers were repressed within 6 hours and mesenchymal genes induced at 24 hours. Snail-1 binding to its target promoters was transient (6-48 hours) despite continued protein expression and it was followed by both transient and long-lasting chromatin changes.
Project description:Epithelial-Mesenchymal Transition (EMT) is thought to contribute to cancer metastasis, but its underlying mechanisms are not well understood. To define early steps in this cellular transformation, we analyzed human mammary epithelial cells with tightly regulated expression of Snail-1, a master regulator of EMT. Following Snail-1 induction, epithelial markers were repressed within 6 hours and mesenchymal genes induced at 24 hours. Snail-1 binding to its target promoters was transient (6-48 hours) despite continued protein expression and it was followed by both transient and long-lasting chromatin changes.
Project description:Human epithelial cancers are defined by a recurrent distribution of specific chromosomal aneuploidies. In our model system, mouse bladder and kidney epithelial cells spontaneously immortalize, transform and become tumorigenic after prolonged culture. We assessed genome and transcriptome alterations and found wide-spread aneuploidy, early transcriptional deregulation, and massive genomic dereguation of the cellular transcriptome. The results reveal a remarkable similarity with genome and transcriptome aberrations detected in human tumorigenesis, hence validating our newly derived cancer models. Epithelial cells were isolated from the C57BL/6 mouse bladder and kidney. These cells underwent spontaneous transformation in culture. We sought to identify the molecuar genomic alterations that occur during the transformation process and to compare these with the changes observed in human bladder and kidney cancers.
Project description:Human epithelial cancers are defined by a recurrent distribution of specific chromosomal aneuploidies. In our model system, mouse bladder and kidney epithelial cells spontaneously immortalize, transform and become tumorigenic after prolonged culture. We assessed genome and transcriptome alterations and found wide-spread aneuploidy, early transcriptional deregulation, and massive genomic dereguation of the cellular transcriptome. The results reveal a remarkable similarity with genome and transcriptome aberrations detected in human tumorigenesis, hence validating our newly derived cancer models. Epithelial cells were isolated from the C57BL/6 mouse bladder and kidney. These cells underwent spontaneous transformation in culture. We sought to identify the molecuar genomic alterations that occur during the transformation process and to compare these with the changes observed in human bladder and kidney cancers.
Project description:We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) for transformation by a single oncogene. The smoke-induced, chromatin changes include initial repressive polycomb marking of genes later manifesting abnormal DNA methylation by 10 months. At this time, cells manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation.
Project description:We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) for transformation by a single oncogene. The smoke-induced, chromatin changes include initial repressive polycomb marking of genes later manifesting abnormal DNA methylation by 10 months. At this time, cells manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation.
