Many components of Wnt/-catenin signaling pathway also play critical roles in mammary tumor development. To study the role of Apc in mammary tumorigensis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-Cre (progenitor) and WAP-cre (lactaing luminal) transgenic mice. Only the K14-cre mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological and molecular heterogeneity, suggesting the progenitor cell origin of these tumors. These tumors harbored truncation mutation in a very defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of -catenin signaling. Our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of -catenin signaling optimal for mammary tumor development.
Genetic mechanisms in Apc-mediated mammary tumorigenesis.
No sample metadata fields
View SamplesTo examine the role of Rb1 in gastrointestinal (GI) tumors we generated mice with an Apc1638N allele, Rbtm2brn floxed alleles, and a villlin-cre transgene (RBVCA). These mice had reduced median survival due to an increase in tumor incidence and multiplicity in the cecum and the proximal colon; they differed from murine intestinal tumors of the Apc1638N type which normally arise solely in the small intestine. We have examined by micro-array analysis three cecal tumors from these mice (probable adenomas), and compared them to three duodenal tumors (probable adenocarcinomas). Expression profiles of duodenal and cecal tumors relative to each other show unique gene subsets up and down regulated. The two tumor types were subsequently shown to differentially regulate distinct sets of genes over expressed in a majority of human colorectal carcinomas.
Loss of Rb1 in the gastrointestinal tract of Apc1638N mice promotes tumors of the cecum and proximal colon.
No sample metadata fields
View SamplesTo characterize the potential molecular pathway(s) affected by iron treatment and identify the one(s) responsible for C3 induction, we performed a whole genome microarray on untreated ARPE-19 cells and cells treated with 250 M FAC for 48h/2d.
Iron-induced Local Complement Component 3 (C3) Up-regulation via Non-canonical Transforming Growth Factor (TGF)-β Signaling in the Retinal Pigment Epithelium.
Cell line, Treatment
View SamplesTankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis and mitosis, offering attractive targets for anti-cancer treatment. Using unbiased combination screening in a large panel of cancer cell lines, we have identified a strong synergy between TNKS and MEK inhibitors in KRAS mutant cancer cells. Our study uncovers a novel function of TNKS in the relief of a feedback loop induced by MEK inhibition on FGFR2 signaling pathway. Moreover, dual inhibition of TNKS and MEK leads to more robust apoptosis and anti-tumor activity both in vitro and in vivo than effects observed by previously reported MEK inhibitor combinations. Altogether, our results show how a novel combination of TNKS and MEK inhibitors can be highly effective in targeting KRAS mutant cancers by suppressing a newly discovered resistance mechanism.
Inhibiting Tankyrases sensitizes KRAS-mutant cancer cells to MEK inhibitors via FGFR2 feedback signaling.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Small Cell Lung Cancer Screen of Oncology Drugs, Investigational Agents, and Gene and microRNA Expression.
Specimen part, Cell line
View SamplesCharacterization of 63 small cell lung cancer (SCLC) cell lines and a comparator set of non-small cell lung cancer and normal counterpart cells, including drug sensitivity testing, gene expression profiling and microRNA expression profiling have been completed. Data and tools for searching these data will be made publicly available through the NCI Developmental Therapeutics Program at http://SCLC.cancer.gov. SCLC is an aggressive, recalcitrant cancer and have seen limited treatment advances in the last 30 years. Drug sensitivity data coupled with the transcription and microRNA profiles of a cohort of SCLC cell lines may help define novel treatment paradigms.
Small Cell Lung Cancer Screen of Oncology Drugs, Investigational Agents, and Gene and microRNA Expression.
Specimen part
View SamplesTo identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathway–specific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Specimen part
View SamplesTo identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Specimen part
View SamplesTo identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Specimen part
View SamplesTo identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Specimen part
View Samples