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Breast Cancer Profiling Project, Drug Sensitivity phase II: Fixed-cell GR measures of 33 breast cell lines and PDX lines to 16 small molecule perturbagens from library plate II. Dataset 2 of 2: Calculated dose response metrics

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SUBMITTER: Caitlin E. Mills

PROVIDER: LDS-1562 | LINCS | 2019-06-27

REPOSITORIES: LINCS

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Project description:Introduction: Breast radiotherapy is currently â??one size fits allâ?? regardless of breast cancer subtype (eg. luminal, basal). However, recent clinical data suggests that radiation response may vary significantly among subtypes. Therefore, current practice leads to over- or under-treatment of women whose tumors are more or less radiation responsive. We hypothesized that this clinical variability may be due, in part, to differences in cellular radiation response. Methods: We exposed 16 biologically-diverse breast tumor cell lines to 0 or 5GY radiation. Microarray analysis was performed on RNA harvested from those cell lines. Samples were run in triplicate. Following quality assessment, differential gene expression analysis was performed using a two-way multiplicative linear mixed-effects model. A candidate radiation response biomarkers with biologically plausible role in radiation response, were identified and confirmed at the RNA and protein level with qPCR and Western blotting assays. Induction in human breast tumors was confirmed in 32 patients with paired pre- and post-radiation tumor samples using IHC and microarray analysis. Quantification of protein was performed in a blinded manner and included positive and negative controls. The objective of our study was to identify genomic determinants of radiation sensitivity using clinical samples as well as breast tumor cell lines. In order to identify differences in the radiation response gene expression profiles of specific breast cancer subtypes, we exposed 16 biologically-diverse breast tumor cell lines to 0 or 5GY radiation. Microarray analysis was performed on RNA harvested from those cell lines. Samples were run in triplicate. Following quality assessment, differential gene expression analysis was performed using a two-way multiplicative linear mixed-effects model. Candidate radiation response biomarker with a biologically plausible role in radiation response, were identified and confirmed at the RNA and protein level with qPCR and Western blotting assays. Induction of the genes of interest were further evaluated and confirmed in human breast tumors in 32 breast cancer patients with paired pre- and post-radiation tumor samples using IHC and microarray analysis assays.

Dataset Information

Breast Cancer Profiling Project, Drug Sensitivity phase II: Fixed-cell GR measures of 33 breast cell lines and PDX lines to 16 small molecule perturbagens from library plate II. Dataset 2 of 2: Calculated dose response metrics

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