title: Activation of the Ig Iα1 promoter by the transcription factor Ets-1 triggers Ig Iα1-Cα1 germline transcription in epithelial cancer cells.
abstract: Immunoglobulins (Igs) are known to be synthesized and secreted only by B lymphocytes. Class switch recombination (CSR) is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initiation is the germline transcription of Ig genes. Surprisingly, recent studies have demonstrated that the Ig genes are also expressed in some epithelial cancer cells; however, the mechanisms underlying how cancer cells initiate CSR and express Igs are still unknown. In this study, we confirmed that the Ig Iα1 promoter in cancer cell lines was activated by the Ets-1 transcription factor, and the activity of the Ig Iα1 promoter and Ig Iα1-Cα1 germline transcription were attenuated after knockdown of Ets-1 by specific small interfering RNAs (siRNA). Furthermore, the expression of Ets-1 and Igα heavy chain in cancer cells was dose dependently upregulated by TGF-β1. These results indicate that activation of the Ig Iα1 promoter by the transcription factor Ets-1 is a critical pathway and provides a novel mechanism for Ig expression in non-B cell cancers.
authors.affiliation: 1] Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Changsha, China [2] Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [3] Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Duan
authors.affiliation: 1] Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Changsha, China [2] Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [3] Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.affiliation: 1] Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Changsha, China [2] Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [3] Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China.
authors.forename: San
authors.initials: S
authors.lastname: Xu
authors.affiliation: 1] Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Changsha, China [2] Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [3] Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Center of Clinical Gene Diagnosis and Therapy, Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Haidan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Immunology, Xiangya Medical College, Central South University, Changsha, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: 1] Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Changsha, China [2] Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [3] Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China.
authors.forename: Duosha
authors.initials: D
authors.lastname: Hu
authors.affiliation: 1] Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Changsha, China [2] Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [3] Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China [4] The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: 1] Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Changsha, China [2] Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [3] Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
mesh_terms: D002277:Carcinoma / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism*; D007127:Immunoglobulin Constant Regions / Q000235:genetics / Q000378:metabolism*; D007137:Immunoglobulin alpha-Chains / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D015854:Up-Regulation
chemical_list: C494041:ETS1 protein, human; D007070:Immunoglobulin A; D007127:Immunoglobulin Constant Regions; D007137:Immunoglobulin alpha-Chains; D050784:Proto-Oncogene Protein c-ets-1; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1