title: Alteration of SMRT tumor suppressor function in transformed non-Hodgkin lymphomas.
abstract: Indolent non-Hodgkin lymphomas are characterized by a prolonged phase that is typically followed by a clinical progression associated with an accelerated clinical course and short survival time. Previous studies have not identified a consistent cytogenetic or molecular abnormality associated with transformation. The development of a transformed phenotype, evolving from the original low-grade component, most likely depends on multiple genetic events, including the activation of synergistic dominant oncogenes and a loss of tumor suppressor gene functions. Complex karyotypes and relatively bad chromosome morphology are typical of transformed non-Hodgkin lymphomas, rendering complete cytogenetic analysis difficult. Here, we report the use of transformed non-Hodgkin lymphoma cell lines and primary samples to identify the involvement of the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) gene that maps at chromosome 12q24 in transformed non-Hodgkin lymphomas. We also show that down-regulation of SMRT in the immortalized "Weinberg's model" cell lines induces transformation of the cells. Assessment of cDNA array profiles should further help us to design a working model for SMRT involvement in non-Hodgkin lymphoma transformation as a novel, nonclassical tumor suppressor.
authors.affiliation: Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Song
authors.forename: Andrei
authors.initials: A
authors.lastname: Zlobin
authors.forename: Pushpankur
authors.initials: P
authors.lastname: Ghoshal
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Christiane
authors.initials: C
authors.lastname: Houde
authors.forename: Sanne
authors.initials: S
authors.lastname: Weijzen
authors.forename: Qun
authors.initials: Q
authors.lastname: Jiang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nacheva
authors.forename: Danny
authors.initials: D
authors.lastname: Yagan
authors.forename: Eric
authors.initials: E
authors.lastname: Davis
authors.forename: Sylvie
authors.initials: S
authors.lastname: Galiegue-Zouitina
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Thomas
authors.initials: T
authors.lastname: Grogan
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.forename: Lionel J
authors.initials: LJ
authors.lastname: Coignet
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation; D017353:Gene Deletion; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D056985:Nuclear Receptor Co-Repressor 2; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C539130:NCOR2 protein, human; D009687:Nuclear Proteins; D056985:Nuclear Receptor Co-Repressor 2; C497570:RBPJ protein, human; D012097:Repressor Proteins