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

Abstract

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. IL1B 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 proIL1B 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 IL1B is detected in some human breast tumor samples. This study demonstrates the presence of nuclear proIL1B in transformed mammary epithelial cells providing the first evidence that IL1B may be a dual function cytokine. © 2010 Landes Bioscience.