Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

Cell Reports

卷:18

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