title: HES1 activation suppresses proliferation of leukemia cells in acute myeloid leukemia.
abstract: Although aberrant Notch activation contributes to leukemogenesis in T cells, the role of Notch pathway in acute myeloid leukemia (AML) remains controversial. To address this issue, we compared the expression levels of its downstream effector HES1 and p21 in bone marrow mononuclear cells (BMNCs) from 30 newly diagnosed AML patients and three AML cell lines to normal BMNCs. The results showed that both of them were downregulated in AML cells. In vitro, induced activation of HES1 by retrovirus in AML cell lines consistently led to AML cell growth arrest and apoptosis induction, which was associated with enhanced p21 expression. Furthermore, overexpression of HES1 in primary AML cells inhibited growth of AML in a xenograft mice model. In conclusion, we demonstrated the tumor suppressor role of HES1 in AML.
authors.affiliation: National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Tian
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Jia
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Yizhuo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D002648:Child; D015536:Down-Regulation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D064593:Heterografts; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D000072056:Transcription Factor HES-1; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020298:U937 Cells
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; D025521:Tumor Suppressor Proteins; C078493:HES1 protein, human