News archives


OCTOBER - DECEMBER 17

JULY - SEPTEMBER 17

APRIL - JUNE 17

JANUARY - MARCH 17

OCTOBER - DECEMBER 16

JULY - SEPTEMBER 16

APRIL - JUNE 16

JANUARY - MARCH 16

OCTOBER - DECEMBER 15

JULY - SEPTEMBER 15

APRIL - JUNE 15

JANUARY - MARCH 15

OCTOBER - DECEMBER 14

JULY - SEPTEMBER 14

APRIL - JUNE 14

JANUARY - MARCH 14

OCTOBER - DECEMBER 13

JULY - SEPTEMBER 13

APRIL - JUNE 13

JANUARY - MARCH 13

OCTOBER - DECEMBER 12

JULY - SEPTEMBER 12

APRIL - JUNE 12

JANUARY - MARCH 12

OCTOBER - DECEMBER 11

JULY - SEPTEMBER 11

APRIL - JUNE 11

JANUARY - MARCH 11

OCTOBER - DECEMBER 10

JULY - SEPTEMBER 10

APRIL - JUNE 10

JANUARY - MARCH 10

OCTOBER - DECEMBER 09

JULY - SEPTEMBER 09

APRIL - JUNE 09

JANUARY - MARCH 09

OCTOBER - DECEMBER 08

JULY - SEPTEMBER 08

APRIL - JUNE 08

JANUARY - MARCH 08

OCTOBER - DECEMBER 07

JULY - SEPTEMBER 07

APRIL - JUNE 07

JANUARY - MARCH 07

 
  current news   Press   selected story    
     
  20th February 2012  
  Ecotropic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors
 
 




Authors
Emilie A. Bard-Chapeaua, Justin Jeyakanib, Chung H. Kokc, Julius Mullera, Belinda Q. Chuaa, Jayantha Gunaratnea, Arsen Batagovd, Piroon Jenjaroenpund, Vladimir A. Kuznetsovd, Chia-Lin Weib, Richard J. D'Andreac, Guillaume Bourqueb, Nancy A. Jenkinsa, and Neal G. Copelanda

a - Institute of Molecular and Cell Biology, Singapore 138673
b - Genome Institute of Singapore, Singapore 138672
c - Acute Leukaemia Laboratory, Centre for Cancer Biology, Department of Hematology, SA Pathology and Department of Hematology and Oncology, The Queen Elizabeth Hospital, Centre for Stem Cell Research, University of Adelaide, Adelaide, SA 5006, Australia
d - Bioinformatics Institute, Singapore 1386721
  
Published in PNAS 19 January 2012 (Epub ahead of print.)

Abstract
Ecotropic viral integration site 1 (EVI1) is an oncogenic duel-domain zinc finger transcription factor that plays an essential role in the regulation of hematopoietic stem cell renewal, and whose overexpression in myeloid leukemia and epithelial cancers is associated with poor patient survival. Despite EVI1’s discovery in 1988 and its emerging role as a dominant oncogene in various types of cancer, few EVI1 target genes are known. This has precluded a clear understanding of exactly how EVI1 contributes to cancer. Using a combination of ChIP-Seq and microarray studies in human ovarian carcinoma cells, we show that the two zinc finger domains of EVI1 bind to DNA independently and regulate different sets of target genes. Strikingly, an enriched fraction of EVI1 target genes are cancer genes or genes associated with cancer. We also show that more than 25% of EVI1 occupied genes contain linked EVI1 and AP1 DNA-binding sites, and provide evidence for a synergistic cooperative interaction between EVI1 and the AP1 family member FOS in the regulation of cell adhesion, proliferation, and colony formation. An increased number of dual EVI1/AP1 target genes are also differentially regulated in late stage ovarian carcinomas, further confirming the importance of the functional cooperation between EVI1 and FOS. Collectively, our data indicate that EVI1 is a multipurpose transcription factor that synergizes with FOS in invasive tumors.


Figure Legend: Model for the cooperation between EVI1 and FOS transcription factors involving a feed-forward loop controlling hallmarks of cancer aggressiveness

For more information on Emilie BARD-CHAPEAU’s research, please see http://www.imcb.a-star.edu.sg/php/fb.php#api