Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis

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概要

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• We previously observed that Pim-3 with serine/threonine kinase activity, was aberrantly expressed in malignant lesions of endoderm-derived organs, liver and pancreas. Because Pim-3 protein was not detected in normal colon mucosal tissues, we evaluated Pim-3 expression in malignant lesions of human colon, another endoderm-derived organ. Pim-3 was detected immunohistochemically in well-differentiated (43/68 cases) and moderately differentiated (23/41 cases) but not poorly differentiated colon adenocarcinomas (0/5 cases). Moreover, Pim-3 proteins were detected in adenoma (35/40 cases) and normal mucosa (26/111 cases), which are adjacent to adenocarcinoma. Pim-3 was constitutively expressed in SW480 cells and the transfection with Pim-3 short hairpin RNA promoted apoptosis. In the same cell line, a pro-apoptotic molecule, Bad, was phosphorylated at Ser112 and Ser 136 sites of phosphorylation that are representative of its inactive form. Ser112 but not Ser136 phosphorylation in this cell line was abrogated by Pim-3 knockdown. Furthermore, in human colon cancer tissues, Pim-3 co-localized with Bad in all cases (9/9) and with phospho-Ser112 Bad in most cases (6/9). These observations suggest that Pim-3 can inactivate Bad by phosphorylating its Ser112 in human colon cancer cells and thus may prevent apoptosis and promote progression of human colon cancer. © 2007 Japanese Cancer Association.

• Oxford University Pressの論文
• 2007-03-10

著者

• OMURA Kenji

  Department of General and Cardiothoracic Surgery, Kanazawa University Graduate School of Medicine

• TSUNEYAMA Koichi

  Department of Human Pathology, Kanazawa University Graduate School of Medicine

• Omura Kenji

  Department Of General And Cardiothoracic Surgery School Of Medicine Kanazawa University

• Omura Kenji

  Department Of General And Cardiothoracic Surgery Kanazawa University Graduate School Of Medicine

• Tsuneyama Koichi

  Department Of Pathology And 21st Century Center Of Excellence Program Toyama University Faculty Of M

• Mukaida Naofumi

  Division Of Molecular Bioregulation Cancer Research Institute Kanazawa University

• Mukaida Naofumi

  Division Of Molecular And Bioregulation Cancer Research Institute Kanazawa University

• Li Ying-yi

  Division Of Molecular Bioregulation Cancer Research Institute Kanazawa University

• POPIVANOVA Boryana

  Division of Molecular Bioregulation, Cancer Research Institute

• ZHENG Huachuan

  Department of Pathology and 21st Century Center of Excellence Program, Toyama University Faculty of

• FUJII Chifumi

  Division of Molecular Bioregulation, Cancer Research Institute

• Popivanova Boryana

  Division Of Molecular Bioregulation Cancer Research Institute

• Tsuneyama Koichi

  Department Of Diagnostic Pathology Graduate School Of Medicine And Pharmaceutical Science University

• Fujii Chifumi

  Division Of Molecular Bioregulation Cancer Research Institute

• Zheng Huachuan

  Department Of Pathology And 21st Century Center Of Excellence Program Toyama University Faculty Of M

• Popivanova Boryana

  Division Of Genetics Cancer Research Institute Kanazawa University

• Li Ying-yi

  Division Of Molecular Bioregulation Cancer Microenvironment Research Program Cancer Research Institute Kanazawa University

• Tsuneyama Koichi

  Department Of Diagnostic Pathology Graduate School Of Medicine And Pharmaceutical Science For Research University Of Toyama

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