title: Bone morphogenetic proteins induce apoptosis in multiple myeloma cells by Smad-dependent repression of MYC.
abstract: Bone morphogenetic proteins (BMPs) have been shown to induce apoptosis and growth arrest in myeloma cells. However, the molecular mechanisms behind these events are not known. The MYC oncogene is a master regulator of cell growth and protein synthesis and MYC overexpression has been proposed to be associated with the progression of multiple myeloma. Here, we show that BMP-induced apoptosis in myeloma cells is dependent on downregulation of MYC. Moreover, the results suggest that targeting the MYC addiction in multiple myeloma is an efficient way of killing a majority of primary myeloma clones. We also found that myeloma cells harboring immunoglobulin (IG)-MYC translocations evaded BMP-induced apoptosis, suggesting a novel way for myeloma cells to overcome potential tumor suppression by BMPs.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Holien
authors.forename: T K
authors.initials: TK
authors.lastname: Våtsveen
authors.forename: H
authors.initials: H
authors.lastname: Hella
authors.forename: C
authors.initials: C
authors.lastname: Rampa
authors.forename: G
authors.initials: G
authors.lastname: Brede
authors.forename: L A G
authors.initials: LA
authors.lastname: Grøseth
authors.forename: M
authors.initials: M
authors.lastname: Rekvig
authors.forename: M
authors.initials: M
authors.lastname: Børset
authors.forename: T
authors.initials: T
authors.lastname: Standal
authors.forename: A
authors.initials: A
authors.lastname: Waage
authors.forename: A
authors.initials: A
authors.lastname: Sundan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D051785:Smad Proteins / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins