Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profling of human breast carcinoma-associated fibroblasts treated with paclitaxol or doxorubicin at therapeutically relevant doses

ABSTRACT: Systemic chemotherapy inflicts cytotoxic injuries on breast carcinoma-associated fibroblasts. We profiled the transcriptomes of human breast carcinoma-associated fibroblasts before and after clinically relevant cytotoxic stimuli induced by chemotheraputic agents. Breast cancer associated fibroblasts (BCAFs) were isolated from the tumor specimen by mechanical dissociation and differential centrifugation. The cells at early passages were treated with paclitaxol or doxorubicin at clinically revealent concentration. Total RNA was extracted from the cells at different time points post-treatment for gene expression profiling.

ORGANISM(S): Homo sapiens

SUBMITTER: Jimmy Su

PROVIDER: E-GEOD-23399 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2-neu) of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs) within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC) and six Her2+. We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER+ cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs may contribute to the more invasive properties and unfavorable prognosis of Her2+ breast cancer. These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer. We isolated CAFs from twenty primary breast cancer samples representing three main subtypes (ER+ (n=7), TNBC (n=7), Her2+ (n=6)) and performed gene expression profile analyses on RNA isolated from these early passage CAFs. Those samples were done in two batches with 4 samples repeated in both batches. One TNBC sample was found to be an outlier and not used in the analysis.

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Gene expression profling of human breast carcinoma-associated fibroblasts treated with paclitaxol or doxorubicin at therapeutically relevant doses

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