Breast Cancer Profiling Project, Drug Sensitivity 1: Fixed-cell GR measures of 35 breast cell lines to 34 small molecule perturbagens. Dataset 2 of 2: Calculated dose response metrics.
Project description:Metastatic lesions are typically not found until patients self-report symptoms or they become radiologically evident. We have developed an engineered metastatic niche (scaffold) that recruits aggressive tumor cells prior to their colonization in other organs. The engineered niche can be monitored for dynamic gene expression, and changes at this site are analogous to those in a native metastatic site (lung) for triple negative breast cancer (4T1 cells). We were able to develop a 10-gene signature from the scaffold that accurately monitors disease progression and recurrence or resistance to resection therapy. This data set acts to dissect the heterogeneity of the cell populations in the engineered and native metastatic niche and identify the cell types that contribute to the success of the signature.
Project description:In previous studies, we identified a distantly related rhomboid homologue gene known as RHBDD2 (Rhomboid domain containing 2) to be markedly overexpressed in the advanced stages of the breast and colorectal cancer diseases. In order to identify RHBDD2 modulated pathways, we analyzed two breast cancer cell lines (MCF7 and T47D) from control and RHBDD2-siRNA transient gene silencing followed by gene expression profiling analysis using the whole genome Toray 3D-GeneTM Human Oligo Chip. Statistical analysis of the Toray's 3D gene expression profiling data identified 566 commonly differentially expressed genes in association to the RHBDD2 knockdown in both breast cancer cell lines. Among the statistically significant over-represented biological process, we found the apoptosis, cell cycle and response to DNA damage process related genes. In addition, categories of genes found in the ubiquitin-proteasome and oxidative phosphorylation were also highly enriched related genes in the commonly deregulated gene list. We further used a lentivirus-based system (shRNA-pLKO.1) for stable silencing of RHBDD2 mRNA in the T47D breast cancer cell line. Using a staurosporine-induced apoptosis model, we demonstrate that RHBDD2 abrogation resulted in an apoptosis-resistant phenotype of T47D breast cancer cell line. These data are in line with a recent study, suggesting that RHBDD2 expression could be up-modulated in response to 5FU-induced apoptosis in colorectal cancer cells. Taken together, these data suggest that RHBDD2 could be involved in the modulation of the programmed cell death in cancer cells. In order to analyze differential gene expression profiling of RHBDD2 silencing and control cells, total RNA was isolated from replicate experiments from two breast cancer cell lines (MCF7 and T47D) derived from the negative control-siRNA and the RHBDD2-siRNA treatments in duplicate experiments.