title: The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer.
abstract: Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is the most important regulator of tumor angiogenesis. However, how transcription factors interact with histone-modifying enzymes to regulate VEGF transcription and tumor angiogenesis remains unclear. Here, we show that transcription factor GATA1 associates with the histone methyltransferase SET7 to promote VEGF transcription and breast tumor angiogenesis. Using chromatin immunoprecipitation assay, we found that GATA1 was required for recruitment of SET7, RNA polymerase II and transcription factor II B to VEGF core promoter. GATA1 enhanced breast cancer cell (MCF7, ZR75-1 and MDA-MB-231)-secreted VEGF via SET7, which promoted vascular endothelial cell (HUVEC) proliferation, migration and tube formation. SET7 was required for GATA1-induced breast tumor angiogenesis and growth in nude mice. Immunohistochemical staining showed that expression of GATA1 and SET7 was upregulated and positively correlated with VEGF expression and microvessel number in 80 breast cancer patients. GATA1 and SET7 are independent poor prognostic factors in breast cancer. Our data provide novel insights into VEGF transcriptional regulation and suggest GATA1/SET7 as cancer therapeutic targets.
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.|Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Liaoning, People's Republic of China.
authors: Yanan
authors: Y
authors: Zhang
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.
authors: Jie
authors: J
authors: Liu
authors: First Affiliated Hospital, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors: Jing
authors: J
authors: Lin
authors: Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Lei
authors: L
authors: Zhou
authors: The Affiliated Hospital of Qing Dao University, Qingdao, People's Republic of China.
authors: Yuhua
authors: Y
authors: Song
authors: Department of General Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors: Bo
authors: B
authors: Wei
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.
authors: Xiaoli
authors: X
authors: Luo
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.|Department of General Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors: Zhida
authors: Z
authors: Chen
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.|The Affiliated Hospital of Qing Dao University, Qingdao, People's Republic of China.
authors: Yingjie
authors: Y
authors: Chen
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.|Department of General Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors: Jiaxiu
authors: J
authors: Xiong
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.
authors: Xiaojie
authors: X
authors: Xu
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.
authors: Lihua
authors: L
authors: Ding
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, People's Republic of China.|Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Liaoning, People's Republic of China.
authors: Qinong
authors: Q
authors: Ye
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D005260:Female; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D057809:HEK293 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012319:RNA Polymerase II / Q000378:metabolism; D035581:Transcription Factor TFIIB / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D035581:Transcription Factor TFIIB; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human; D012319:RNA Polymerase II
keywords: GATA1; SET7; VEGF; angiogenesis; tumor growth