Regulatory network controlling tumor-promoting inflammation in human cancers [ChIP-seq]

Using an inducible, inflammatory model of breast cellular transformation, we describe the transcriptional regulatory network mediated by STAT3, NF-kB, and AP-1 factors on a genomic scale. These regulators form transcriptional complexes that directly regulate the expression of hundreds of genes in oncogenic pathways, such as cell proliferation, metastasis, angiogenesis, apoptosis and metabolism, via a positive feedback loop. This inflammatory feedback loop and associated network, which function to various extents in many types of cancer cells and patient tumors, is the basis for an “inflammation” index that defines cancer types by functional criteria. The inflammation index is negatively correlated with expression of genes involved in DNA metabolism, and transformation is associated with genome instability. Inflammatory tumors are preferentially associated with infiltration immune cells that might be recruited to the site of the tumor via inflammatory molecules produced by the cancer cells. Overall design: ChIP-seq for STAT3, NF-kb, JUN, JUNB and FOS before and after MCF10A-ER-Src cell transformation