title: Notch signaling inhibits the growth of the human chronic myeloid leukemia cell line K562.
abstract: Notch signaling functions in the development of some types of leukemia and lymphoma, but the relationship between Notch signaling and chronic myeloid leukemia (CML) remains to be elucidated. In this study, we examined the expression of Notch receptors and ligands in the human CML cell line K562. When the active form of Notch1, the Notch intra-cellular domain (NIC), was over-expressed in K562, the proliferation of K562 was mildly but significantly inhibited, accompanied by increased Hes1 mRNA level. On the other hand, when Notch signaling was attenuated by over-expression of a dominant-negative RBP-J, RBP-J(R218H), in K562 cells, the proliferation of K562 was increased. Moreover, we found that activation of Notch signaling inhibited while repression of Notch signaling promoted the colony-forming activity of K562 cells. We examined cell cycle-related molecules in K562 transfected with NIC or RBP-J(R218H), and found that the protein level of the retinoblastoma gene product (the Rb protein) was induced in K562 expressing NIC, and down-regulated in K562 expressing RBP-J(R218H). These data suggest that the Notch signaling may function as a tumor inhibitor in human CML cells.
authors.affiliation: Department of Hematology, Tangdu Hospital, Xi'an 710038, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yin
authors.forename: Feng-Yun
authors.initials: FY
authors.lastname: Fan
authors.forename: Xing-Bin
authors.initials: XB
authors.lastname: Hu
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Hou
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ying-Min
authors.initials: YM
authors.lastname: Liang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
mesh_terms: D015153:Blotting, Western; D002455:Cell Division; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology*; D051880:Receptors, Notch / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D051880:Receptors, Notch; D016160:Retinoblastoma Protein