title: Tumors with nonfunctional retinoblastoma protein are killed by reduced γ-tubulin levels.
abstract: In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway. Here, we describe that RB1 and γ-tubulin proteins moderate each other's expression by binding to their respective gene promoters. Simultaneous reduction of RB1 and γ-tubulin protein levels results in an E2F1-dependent up-regulation of apoptotic genes such as caspase 3. We report that in various tumors types, there is an inverse correlation between the expression levels of γ-tubulin and RB1 and that in tumor cell lines with a nonfunctioning RB1, reduction of γ-tubulin protein levels leads to induction of apoptosis. Thus, the RB1/γ-tubulin signal network can be considered as a new target for cancer treatment.
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Ehlén
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Catalina A
authors.initials: CA
authors.lastname: Rosselló
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: von Stedingk
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Greta
authors.initials: G
authors.lastname: Höög
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Elise
authors.initials: E
authors.lastname: Nilsson
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Pettersson
authors.affiliation: Department of Clinical Sciences, Pathology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden. Electronic address: maria.alvarado-kristensson@med.lu.se.
authors.forename: Maria
authors.initials: M
authors.lastname: Alvarado-Kristensson
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D016160:Retinoblastoma Protein; D014404:Tubulin; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3