title: Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate cancer.
abstract: B-cell leukemia 3 (Bcl-3) is a member of the inhibitor of κB family, which regulates a wide range of biological processes by functioning as a transcriptional activator or as a repressor of target genes. As high levels of Bcl-3 expression and activation have been detected in different types of human cancer, Bcl-3 has been labeled a proto-oncogene. Our study uncovered a markedly upregulated Bcl-3 expression in human prostate cancer (PCa), where inflammatory cell infiltration was observed. Elevated Bcl-3 expression in PCa was dependent on the proinflammatory cytokine interleukin-6-mediated STAT3 activation. Microarray analyses, using Bcl-3 knockdown in PCa cells, identified the inhibitor of DNA-binding (Id) family of helix-loop-helix proteins as potential Bcl-3-regulated genes. Bcl-3 knockdown reduced the abundance of Id-1 and Id-2 proteins and boosted PCa cells to be more receptive to undergoing apoptosis following treatment with anticancer drug. Our data imply that inactivation of Bcl-3 may lead to sensitization of cancer cells to chemotherapeutic drug-induced apoptosis, thus suggesting a potential therapeutic strategy in PCa treatment.
authors.affiliation: Center for Molecular Tumor Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Ahlqvist
authors.forename: K
authors.initials: K
authors.lastname: Saamarthy
authors.forename: A S
authors.initials: AS
authors.lastname: Syed Khaja
authors.forename: A
authors.initials: A
authors.lastname: Bjartell
authors.forename: R
authors.initials: R
authors.lastname: Massoumi
mesh_terms: D000081242:B-Cell Lymphoma 3 Protein; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics*; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D052003:NF-kappa B p52 Subunit / Q000502:physiology; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D011519:Proto-Oncogenes; D050796:STAT3 Transcription Factor / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C497453:ID1 protein, human; C497450:ID2 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D015850:Interleukin-6; C000715470:MAS1 protein, human; D052003:NF-kappa B p52 Subunit; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; D014157:Transcription Factors