Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of rat 3Y1 embryonic fibroblasts to identify MUC1-induced transcriptional alterations

ABSTRACT: The MUC1 oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis and extracellular matrix remodeling. A set of experimentally-derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature (MTS) predicts significant decreases in both disease-free and overall survival in patients with breast (n = 295) and lung (n = 442) cancers. The data demonstrate that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients. Experiment Overall Design: To investigate the genes associated with MUC1-CD-induced transformation and tumorigenesis, we performed expression profiling of 3Y1/Vector (empty vector-transfected 3Y1) and 3Y1/MUC1-CD (MUC1-CD-transfected 3Y1) cells growing in vitro, and of 3Y1/MUC1-CD cells growing as tumor xenografts in athymic mice. Cells grown in vitro or as tumor xenografts were lysed to collect total RNA for hybridization with GeneChipÂ® Rat Genome 230 2.0 Arrays.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Sean Pravin Pitroda

PROVIDER: E-GEOD-14337 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment.

Pitroda Sean P SP Khodarev Nikolai N NN Beckett Michael A MA Kufe Donald W DW Weichselbaum Ralph R RR

Proceedings of the National Academy of Sciences of the United States of America 20090316 14

The mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in human breast cancers. Although MUC1 modulates the activity of estrogen receptor alpha (ER), there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for breast cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of genes involved in cholesterol and fatty acid metaboli ...[more]

PMID: 19289846

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Project description:MUC1 is a tumor-associated antigen that is aberrantly expressed in cancer and inflammatory bowel disease (IBD). Even though immune cells express low MUC1 levels, their modulations of MUC1 are important in tumor progression. Consistent with previous clinical data that show increased myeloid-derived suppressor cells (MDSCs) in IBD, we now show that down-regulation of MUC1 on hematopoietic cells increases MDSCs in IBD, similar to our data in tumor-bearing mice. We hypothesize that MDSC expansion in IBD is critical for tumor progression. In order to mechanistically confirm the linkage between Muc1 down-regulation and MDSC expansion, we generated chimeric mice that did not express Muc1 in the hematopoietic compartment (KOM-bM-^FM-^RWT). These mice were used in 2 models of colitis and colitis-associated cancer (CAC) and their responses were compared to wildtype chimeras (WTM-bM-^FM-^RWT). KOM-bM-^FM-^RWT mice show increased levels of MDSCs during colitis that was responsible for the larger colon tumors that eventually developed in these mice. Using microarray and qRT-PCR analysis, we observed increased pro-tumorigenic signaling in the colons of KOM-bM-^FM-^RWT mice during colitis as compared to WTM-bM-^FM-^RWT mice. Our RNA (microarray and qRT-PCR analysis) and protein analysis demonstrate increased up-regulation of metalloproteinases, collagenases, defensins, complements, growth factors, cytokines and chemokines in KOM-bM-^FM-^RWT mice as compared to WTM-bM-^FM-^RWT mice. Antibody-mediated depletion of MDSCs in mice during colitis reduced colon tumor formation during CAC. Development of CAC is a serious complication of colitis and our data highlight MDSCs as a targetable link between inflammation and cancer. A total of 12 samples were analysed. RNA was made from the mucosa of the colon of WTM-bM-^FM-^RWT and KOM-bM-^FM-^RWT mice that were either untreated or treated with azoxymethane (AOM) and dextran sodium sulfate (DSS). There are 4 groups, n=3 for each group: untreated WTM-bM-^FM-^RWT mice, untreated KOM-bM-^FM-^RWT mice, AOM+DSS treated WTM-bM-^FM-^RWT mice, AOM+DSS treated KOM-bM-^FM-^RWT mice = 12 samples in total.

Dataset Information

Transcription profiling of rat 3Y1 embryonic fibroblasts to identify MUC1-induced transcriptional alterations

Publications

MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment.

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