Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma. |
| |
| Authors: | J Asp S Inerot J A Block A Lindahl |
| |
| Affiliation: | 1. Department of Clinical Chemistry and Transfusion Medicine, Research Center for Endocrinology and Metabolism, Institution of Laboratory Medicine, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden;2. Section of Orthopaedic Oncology, Department of Orthopaedics, Sahlgrenska University Hospital, Göteborg, Sweden;3. Section of Rheumatology, Department of Internal Medicine, Rush-Presbyterian-St. Luke''s Medical Center, Chicago, IL, USA;1. University of the Azores, OKEANOS Research Unit, Institute of Marine Research (IMAR), Horta, Azores, Portugal;2. Marine and Environmental Sciences Centre (MARE), Azores, Portugal;3. Sustainable Fisheries Partnership Foundation (SFP), Honolulu, USA;4. European Commission, Joint Research Centre (JRC), Ispra, Italy;5. Instituto Português do Mar e da Atmosfera (IPMA), Lisbon, Portugal;1. Department of Surgery and Perioperative Care, Dell Medical School at the University of Texas, Austin, TX, USA;2. Self-employed, Saint Joseph, MI, USA;1. Primary Care Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK;2. Institute of Public Health, School of Clinical Medicine, University of Cambridge, Cambridge, UK;3. Research Department of Epidemiology and Public Health, University College London, London, UK;4. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK;5. MRC-PHE Centre for Environment and Health, King’s College London, London, UK;1. Smart Manufacturing Technology R&D Group, Korea Institute of Industrial Technology (KITECH), Daegu 42994, Republic of Korea;2. School of Mechanical Engineering, Kyungpook National University, Daegu 41566, Republic of Korea;1. Department Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA;2. Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark;3. Section of Biomolecular Sciences, Department of Biology, University of Copenhagen, Denmark;4. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-2517, USA;5. CSIRO Manufacturing, CSIRO, Clayton, VIC 3168, Australia;6. Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA;7. Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158-2517, USA;8. Department of Bioengineering, Stanford University, Stanford, CA 94305, USA;9. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA;1. College of Engineering, The Ohio State University, Columbus, OH 43212, USA;2. Department of Mechanical Engineering, McMaster University, Hamilton, ON L8S 4L7, Canada;3. Department of Mechanical Engineering, Clemson University, Clemson, SC 29634, USA;4. State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai, China;5. Department of Materials Manufacturing, Ford Motor Company, Dearborn, MI 48124, USA |
| |
| Abstract: | The G1 regulatory pathway involving p16, pRb and cdk4 in the cell cycle has been investigated in human chondrosarcoma. The protein expression of p16, pRb and cdk4 was analyzed by Western blot in cultured cells from eight chondrosarcomas and in two chondrosarcoma cell lines. Both cell lines and one other sample were negative for p16. Moreover, one of the cell lines was pRb-negative and showed a high expression of cdk4 as well. In the other cell line and in three other samples pRb of expected size were detected in addition to a shorter form of the protein. To further investigate the reasons for down-regulation of the p16 protein, the p16-coding gene CDKN2 was analyzed by polymerase chain reaction (PCR), methyl-specific PCR (MSP) and sequencing in all tumor samples as well as in corresponding tumor tissues from three of the samples. The p16-negative samples were all found to have homozygous deletion of CDKN2. Another sample showed partial gene methylation and a heterozygous position in codon 148 was detected in one sample. The same base substitution was also found in two of the tissue samples. Finally, cytogenetic analysis of the samples with homozygously deleted CDKN2 revealed multiple structural abnormalities in all three cases. In conclusion, the p16/pRb/cdk4 pathway may play an important role in the pathogenesis of some chondrosarcomas. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
