Abstract
This review addresses genes differentially expressed in the mammary gland transcriptome during the progression of mammary carcinogenesis in BALB/c mice that are transgenic for the rat neu (ERBB2, or HER-2/neu) oncogene (BALB-neuT664V-E mice). The Ingenuity knowledge database was used to characterize four functional association networks whose hub genes are directly linked to inflammation (specifically, the genes encoding IL-1β, tumour necrosis factor, interferon-γ, and monocyte chemoattractant protein-1/CC chemokine ligand-2) and are increasingly expressed during such progression. In silico meta-analysis in a human breast cancer dataset suggests that proinflammatory activation in the mammary glands of these mice reflects a general pattern of human breast cancer.
Highlights
Inflammation, the archetypal response to invasion, has evolved as a local protective response to life-threatening invasion; it is required to be rapid and devastating, sometimes regardless of the cost to the host
This review addresses genes differentially expressed in the mammary gland transcriptome during the progression of mammary carcinogenesis in BALB/c mice that are transgenic for the rat neu (ERBB2, or HER-2/neu) oncogene (BALB-neuT664V-E mice)
The Ingenuity knowledge database was used to characterize four functional association networks whose hub genes are directly linked to inflammation and are increasingly expressed during such progression
Summary
Inflammation, the archetypal response to invasion, has evolved as a local protective response to life-threatening invasion; it is required to be rapid and devastating, sometimes regardless of the cost to the host. The presence of GATMs associated with TNF, IL-1β, IFN-γ, and MCP-1/CCL2 hub genes, and characterized by human orthologs (a total of 77 genes), was sought in the dataset reported by Chin and coworkers [38] This is one of the largest collections of breast cancer samples (n = 118) analyzed by microarray and for which the clinical outcome is known. The work reported by Chin [38] and Neve [39] and their colleagues offers a unique opportunity to discriminate between transcripts that belong to the tumour microenvironment and those associated with tumour cells Taking advantage of these transcriptional profiles [38,39] and specific data mining techniques [40], one can determine whether a set of genes shares little expression similarity between tumour specimens and cell lines. CCL, CC chemokine ligand; GATM, gene associated with mammary tumour microenvironment; IFN, interferon; IL, interleukin; MCP, monocyte chemoattractant protein; TNF, tumour necrosis factor. It should be noted that the gene encoding MCP-1/ CCL2 is the only one of the four hub genes (those encoding IFN-γ, TNF, IL-1β and MCP-1/CCL2) that constantly exhibit relatively high levels of expression (Figure 8)
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