Expression of focal adhesion kinase in uveal melanoma and the effects of Hsp90 inhibition by 17-AAG |
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| Institution: | 1. Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada;2. Ocular Pathology Department, Anatomy Pathology Institute, University Central of Venezuela, Caracas, Venezuela;3. Department of Ophthalmology, São Paulo Federal University – UNIFESP, São Paulo, Brazil;1. Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226001, PR China;2. Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China;3. Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China;4. Department of Pathology, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China;1. Department of Anatomic Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;2. Department of Anatomic Pathology, AC Camargo Cancer Center, São Paulo, Brazil;1. Max Planck Institute of Psychiatry, Munich, Germany;2. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany;3. Laboratory of Neuroproteomics, Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil;1. Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea;2. Department of Pathology, Dong-A University College of Medicine, Busan, South Korea;3. Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea;4. Department of Nuclear Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea;5. Division of Gastroenterology, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea;6. Department of Clinical Laboratory Science, Dong-Eui Institute of Technology, Busan, South Korea;1. Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA;2. Array BioPharma Inc., Boulder, CO, USA |
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| Abstract: | IntroductionFocal adhesion kinase (FAK) is implicated in tumor progression and metastatic cascade, and has been shown to be overexpressed in a variety of human cancers. However, the role of FAK in human uveal melanoma (UM) is not well defined. The purpose of this study was to evaluate the expression of FAK in UM tumors and normal eyes, and to determine the effect of Hsp90 inhibition on FAK expression in UM cells.MethodsFAK expression was assessed in 39 UM specimens, FAKpY397] expression was assessed in 51 UM specimens, and both FAK and FAKpY397] expression were assessed in 20 normal eyes. The expression of FAK and FAKpY397] was detected by Western blot in five UM cell lines after treatment with 10 μmol/L of 17-AAG.ResultsFAK was positive in 87.2% and FAKpY397] in 90% of UM specimens. Low FAK expression was detected in non-tumor structures and in normal eyes. The cell lines with the most proliferative, invasive phenotype (92.1, SP6.5 and MKT-BR) displayed high expression of FAKpY397], and the levels of FAK and FAKpY397] were decreased in the presence of 17-AAG starting with 24 h of exposure.ConclusionFAK and FAKpY397] were overexpressed in human UM tumors compared to normal ocular tissue and high levels of FAKpY397] were seen in the most aggressive UM cell lines. Hsp90 inhibition led to downregulation of FAK expression. We propose a role for FAK in the pathogenesis of UM. Future studies are needed to explore the use of Hsp90 inhibitors as a feasible approach for modulating FAK in UM. |
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| Keywords: | Focal adhesion kinase Uveal melanoma Hsp90 Immunohistochemistry |
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