title: Transcription factors E2A, FOXO1 and FOXP1 regulate recombination activating gene expression in cancer cells.
abstract: It has long been accepted that immunoglobulins (Igs) were produced by B lymphoid cells only. Recently Igs have been found to be expressed in various human cancer cells and promote tumor growth. Recombination activating gene 1 (RAG1) and RAG2, which are essential enzymes for initiating variable-diversity-joining segment recombination, have also been found to be expressed in cancer cells. However, the mechanism of RAG activation in these cancer cells has not been elucidated. Here, we investigated the regulatory mechanism of RAG expression in four human cancer cell lines by analyzing transcription factors that induce RAG activation in B cells. By RT-PCR, Western blot and immunofluorescence, we found that transcription factors E2A, FOXO1 and FOXP1 were expressed and localized to the nuclei of these cancer cells. Over-expression of E2A, FOXO1 or Foxp1 increased RAG expression, while RNA interference of E2A, FOXO1 or FOXP1 decreased RAG expression in the cancer cells. Chromatin immunoprecipitation experiments showed acetylation of RAG enhancer (Erag) and E2A, FOXO1 or FOXP1 were bound to Erag in vivo. These results indicate that in these cancer cells the transcription factors E2A, FOXO1 and FOXP1 regulate RAG expression, which initiates Ig gene rearrangement much in the way similar to B lymphocytes.
authors.affiliation: Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Zhengshan
authors.initials: Z
authors.lastname: Chen
authors.forename: Yanna
authors.initials: Y
authors.lastname: Xiao
authors.forename: Junjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Changchun
authors.initials: C
authors.lastname: Ma
authors.forename: Jin
authors.initials: J
authors.lastname: Luo
authors.forename: Yamei
authors.initials: Y
authors.lastname: Qiu
authors.forename: Guowei
authors.initials: G
authors.lastname: Huang
authors.forename: Christine
authors.initials: C
authors.lastname: Korteweg
authors.forename: Jiang
authors.initials: J
authors.lastname: Gu
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011995:Recombination, Genetic / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D051740:Ikaros Transcription Factor; D016328:NF-kappa B; D009687:Nuclear Proteins; D012097:Repressor Proteins; C085126:FOXO1 protein, human; C486626:FOXP1 protein, human; C499311:RAG2 protein, human; C407909:TCF3 protein, human; C064658:RAG-1 protein