title: High expression of BCL3 in human myeloma cells is associated with increased proliferation and inferior prognosis.
abstract: BACKGROUND
  BCL3 is a putative oncogene encoding for a protein belonging to the inhibitory kappaB-family. We experienced that this putative oncogene was a common target gene for growth-promoting cytokines in myeloma cell lines.
  
  
  METHODS
  Gene expression of BCL3 was studied in 351 newly diagnosed myeloma patients, 12 patients with smouldering myeloma, 44 patients with monoclonal gammopathy of undetermined significance and 22 healthy individuals. Smaller material of samples was included for mRNA detection by RT-PCR, protein detection by Western blot and immunohistochemistry, and for cytogenetic studies. A total of eight different myeloma cell lines were studied.
  
  
  RESULTS
  Bcl-3 was induced in myeloma cell lines by interleukin (IL)-6, IL-21, IL-15, tumor necrosis factor-alpha and IGF-1, and its upregulation was associated with increased proliferation of the cells. In a population of 351 patients, expression levels of BCL3 above 75th percentile were associated with shorter 5-yr survival. When this patient population was divided into subgroups based on molecular classification, BCL3 was significantly increased in a poor risk subgroup characterized by overexpression of cell cycle and proliferation related genes. Intracellular localization of Bcl-3 was dependent on type of stimulus given to the cell.
  
  
  CONCLUSIONS
  BCL3 is a common target gene for several growth-promoting cytokines in myeloma cells and high expression of BCL3 at the time of diagnosis is associated with poor prognosis of patients with multiple myeloma (MM). These data may indicate a potential oncogenic role for Bcl-3 in MM.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Anne-Tove
authors.initials: AT
authors.lastname: Brenne
authors.forename: Unn-Merete
authors.initials: UM
authors.lastname: Fagerli
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
authors.forename: Thea Kristin
authors.initials: TK
authors.lastname: Våtsveen
authors.forename: Torstein Baade
authors.initials: TB
authors.lastname: Rø
authors.forename: Hanne
authors.initials: H
authors.lastname: Hella
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Anders
authors.initials: A
authors.lastname: Sundan
authors.forename: Magne
authors.initials: M
authors.lastname: Børset
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
mesh_terms: D000081242:B-Cell Lymphoma 3 Protein; D016022:Case-Control Studies; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D016207:Cytokines / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D016207:Cytokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors