Cell Reports | 卷:18 |
Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer | |
Koen M.A. Dreijerink1  Elgene Lim1  David Chi1  Prakash K. Rao1  Charles Y. Lin1  Alba Font-Tello1  Jennifer Cook1  Myles Brown1  Henry W. Long1  Jaime Reyes1  Anna C. Groner1  Lei Gu2  Wouter de Laat3  Erica S.M. Vos3  | |
[1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston 02215, MA, USA; | |
[2] Division of Newborn Medicine, Children’s Hospital Boston and Department of Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; | |
[3] Hubrecht Institute-KNAW and University Medical Center, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; | |
关键词: breast cancer; MEN1; tumor suppressor; oncogene; transcription; epigenetics; menin; histone H3K4 trimethylation; enhancer; | |
DOI : 10.1016/j.celrep.2017.02.025 | |
来源: DOAJ |
【 摘 要 】
While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER+ cells. In primary mammary cells, MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell-type-specific functions of MEN1 and inform the development of menin-directed treatments for breast cancer.
【 授权许可】
Unknown