title: Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis.
abstract: 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 Ser(112) and Ser(136) sites of phosphorylation that are representative of its inactive form. Ser(112) but not Ser(136) 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-Ser(112)Bad in most cases (6/9). These observations suggest that Pim-3 can inactivate Bad by phosphorylating its Ser(112) in human colon cancer cells and thus may prevent apoptosis and promote progression of human colon cancer.
authors.affiliation: Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University 13-1 Takara-machi, Kanazawa 920-0934, Japan.
authors.forename: Boryana Konstantinova
authors.initials: BK
authors.lastname: Popivanova
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Li
authors.forename: Huachuan
authors.initials: H
authors.lastname: Zheng
authors.forename: Kenji
authors.initials: K
authors.lastname: Omura
authors.forename: Chifumi
authors.initials: C
authors.lastname: Fujii
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
mesh_terms: D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051025:bcl-Associated Death Protein; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases