title: Involvement of Mediator complex in malignancy.
abstract: Mediator complex (MED) is an evolutionarily conserved multiprotein, fundamental for growth and survival of all cells. In eukaryotes, the mRNA transcription is dependent on RNA polymerase II that is associated to various molecules like general transcription factors, MED subunits and chromatin regulators. To date, transcriptional machinery dysfunction has been shown to elicit broad effects on cell proliferation, development, differentiation, and pathologic disease induction, including cancer. Indeed, in malignant cells, the improper activation of specific genes is usually ascribed to aberrant transcription machinery. Here, we focus our attention on the correlation of MED subunits with carcinogenesis. To date, many subunits are mutated or display altered expression in human cancers. Particularly, the role of MED1, MED28, MED12, CDK8 and Cyclin C in cancer is well documented, although several studies have recently reported a possible association of other subunits with malignancy. Definitely, a major comprehension of the involvement of the whole complex in cancer may lead to the identification of MED subunits as novel diagnostic/prognostic tumour markers to be used in combination with imaging technique in clinical oncology, and to develop novel anti-cancer targets for molecular-targeted therapy.
authors.affiliation: Institute of Diagnostic and Nuclear Development (SDN), IRCCS, Via E. Gianturco 113, 80143 Naples, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Schiano
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. Electronic address: amelia.casamassimi@unina2.it.
authors.forename: Amelia
authors.initials: A
authors.lastname: Casamassimi
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Rienzo
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: de Nigris
authors.affiliation: U.O.C. Immunohematology, Transfusion Medicine and Transplant Immunology [SIMT], Regional Reference Laboratory of Transplant Immunology [LIT], Azienda Universitaria Policlinico (AOU), 1st School of Medicine, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Sommese
authors.affiliation: Institute of Diagnostic and Nuclear Development (SDN), IRCCS, Via E. Gianturco 113, 80143 Naples, Italy; Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy; U.O.C. Immunohematology, Transfusion Medicine and Transplant Immunology [SIMT], Regional Reference Laboratory of Transplant Immunology [LIT], Azienda Universitaria Policlinico (AOU), 1st School of Medicine, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
mesh_terms: D056745:Cyclin C / Q000502:physiology; D056850:Cyclin-Dependent Kinase 8 / Q000502:physiology; D006801:Humans; D056892:Mediator Complex / Q000502:physiology*; D056913:Mediator Complex Subunit 1 / Q000502:physiology; D009369:Neoplasms / Q000209:etiology*
chemical_list: C503674:CCNC protein, human; D056745:Cyclin C; C538855:MED1 protein, human; C460107:MED12 protein, human; C496877:MED28 protein, human; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8
keywords: Biomarkers; Cancer; Mediator complex; Transcription; Tumorigenesis