title: Impact of MYC on malignant behavior.
abstract: MYC, a member of the helix-loop-helix leucine zipper family of nuclear transcription factors, is a potent proto-oncogene primarily identified as the target of the t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. Activation of the MYC gene in normal cells both results in enhanced cellular proliferation and up-regulation of pro-apoptotic pathways, reflecting the tight regulation of the molecule in the normal cellular system. In the process of transformation, these secondary inhibitory functions of the MYC molecule have to be overcome through secondary mutations of the MYC gene itself and/or by abrogating the inhibitory effects of physiological regulators and/or repressors of proliferation such as BCL2, BCL6, BLIMP1, or others. Most aggressive lymphomas, therefore, harbor additional oncogenic alterations that cooperate with MYC deregulation, with different alterations identified in human solid or hematological tumors. These alterations are likely to counteract the pro-apoptotic function of MYC. MYC gene alterations in diffuse large B-cell lymphomas and in B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma are frequently associated with BCL2 or/and BCL6 translocations conferring a very aggressive behavior. This review summarizes inherent factors of the biology and function of MYC important in the process of transformation, especially taking account the interdependence of MYC on various cellular networks that have to be co-deregulated to achieve the full malignant phenotype.
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: German
authors.initials: G
authors.lastname: Ott
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D002470:Cell Survival; D053263:Gene Regulatory Networks; D006801:Humans; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc