Genomic profiling of C/EBPβ2 transformed mammary epithelial cells: a role for nuclear interleukin-1β.
C/EBPβ is essential for mammary gland growth and development and has been associated with poor prognosis in breast cancer. Overexpression of C/EBPβ2 in MCF10A cells results in a variety of cancer phenotypes including EMT and ErbB independence. IL1β is dramatically upregulated in MCF10A-C/EBPβ2 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 proIL1β 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/EBPβ2 cells. Moreover, nuclear IL1β is detected in some human breast tumor samples. This study demonstrates the presence of nuclear proIL1β in transformed mammary epithelial cells providing the first evidence that IL1β may be a dual function cytokine.
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Alisha
A
Russell
Braden
B
Boone
Aixiang
A
Jiang
Linda
L
Sealy
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics; D015398:Signal Transduction
D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; D002843:Chromatin; D053583:Interleukin-1beta; D011498:Protein Precursors; D053574:Receptors, Interleukin-1 Type II