Genomic profiling of C/EBPbeta2 transformed mammary epithelial cells: a role for nuclear interleukin-1beta.

摘要

C/EBPbeta is essential for mammary gland growth and development and has been associated with poor prognosis in breast cancer. Overexpression of C/EBPbeta2 in MCF10A cells results in a variety of cancer phenotypes including EMT and ErbB independence. IL1beta is dramatically upregulated in MCF10A-C/EBPbeta2 cells but there is little, if any, processing to the mature 17 kD form. Although proIL1b has previously been considered to be biologically inactive, we demonstrate proIL1b is not only localized to the nucleus, but is also tightly associated with the chromatin. We show that proIL1beta is bound at specific locations in the genome and is positioned in such a way to play a role in the cancer phenotypes observed in MCF10A-C/EBPbeta2 cells. Moreover, nuclear IL1beta is detected in some human breast tumor samples. This study demonstrates the presence of nuclear proIL1beta in transformed mammary epithelial cells providing the first evidence that IL1beta may be a dual function cytokine.