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Identification of significant gene regulations for breast cancer from human tissues

ABSTRACT: To discover individual genes with potential diagnostic and therapeutic utilities, we use gene expression profiling from real patient tissues to identify significantly regulated genes out of a broad coverage of human transcriptome. We use Agilent gene expression microarray technologies to measure gene expressions of 32 cancerous and normal tissues from breast cancer patients. Total RNAs were extracted and analyzed using Agilent microarray technologies. The whole genome expression profiling has been proformed and several significantly differently expressed genes (such as HS3ST4, MMP1, MMP11) were quatified by qPCR to verify their up/down-regulations, leading to discovery of important genes related to breast cancer metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE57297 | GEO | 2014/05/08

SECONDARY ACCESSION(S): PRJNA246209

REPOSITORIES: GEO

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Project description:Proliferation, dedifferentiation, loss of cell-cell contacts and angiogenesis are among the first steps of the metastasis cascade. The complex molecular pathways associated with these events in canine mammary tumors are mostly unknown and the value of this spontaneous canine tumor as a comparative model for human breast cancer is therefore still under debate. Messenger RNA profiles of lymph-node positive canine mammary carcinomas and normal mammary glands of the same dogs were compared by microarray analysis to elucidate molecular pathways associated with metastatic progression. Differential gene expression was analyzed by gene set enrichment and pathway analysis and compared with the gene expression data of human breast cancer. Metastatic canine carcinomas had 1,312 significantly differentially expressed genes when compared to the corresponding normal mammary gland. This expression profile included a significantly increased expression of cell division and extracellular matrix invasion genes (MMP1, MMP11, MMP13, SERPINE1, TFPI2, TIMP3). In contrast, genes associated with epithelial differentiation (EGF, EGFR, KRT17, MAP2K6, STAT5), cell adhesion (CLDN5, CLDN8, CTNNAL1, MCAM, MUC1, PECAM1) and angiogenesis (ANGPT2, ANGPTL1, ANGPTL2, ANGPTL4, FGFR1, FIGF, TIE1) were mostly down-regulated. Interestingly, tumors had a significant decrease in membrane receptors and growth factor pathway gene expression (EGFR, FGFR1, GHR, LYVE1, PDGFR, PDGFR, TGFBR, TIE1), indicating a potential independence from these proliferative stimuli. Several of the identified deregulated pathways overlap with gene expression profiles of human breast cancer. Gene expression profiling of metastatic carcinomas therefore identified complex molecular pathways and functional gene families that are deregulated during malignant progression in the tumors. This study provides new insights into canine mammary tumor metastasis and suggests that canine mammary tumors may serve as a valuable model for the human disease.

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Identification of significant gene regulations for breast cancer from human tissues

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