title: p53 overexpression increases chemosensitivity in multidrug-resistant osteosarcoma cell lines.
abstract: OBJECTIVE
  Multidrug resistance (MDR) is a major obstacle to the successful treatment of osteosarcoma with chemotherapy. Effectiveness of cancer therapy correlates with the ability to induce a p53-dependent apoptotic response. p53 is a tumor suppressor gene that is mutated in 22 % of osteosarcomas. While impaired p53 has been implicated in the oncogenesis of osteosarcoma, it is unclear whether overexpression of wild-type p53 can increase chemosensitivity in MDR osteosarcoma cells.
  
  
  METHODS
  We transfected a plasmid encoding the wild-type p53 gene to MDR osteosarcoma cell lines, which have different p53 statuses, U-2OSR2 with wild-type p53 (Wt-p53) and KHOSR2 with mutant p53 (Mt-p53), and determined the effect of p53 overexpression on chemosensitivities.
  
  
  RESULTS
  Both of the U-2OSR2 and KHOSR2 cell lines displayed similar trends in p53-induced drug sensitivities. However, it seems that the impact of p53 overexpression is different based on the differential intrinsic p53 status in these cell lines. In the KHOSR2 cell line (Mt-p53), overexpression of p53 up-regulates the expression of pro-apoptotic protein p21 and Bax, while in the U-2OSR2 cell line (Wt-p53), overexpression of p53 down-regulates IGF-1r expression significantly.
  
  
  CONCLUSIONS
  These results demonstrated that transfection of wild-type p53 increases chemosensitivity either through inhibiting IGF-1r or through increasing the expression of pro-apoptotic proteins p21 and Bax in human MDR osteosarcoma cell lines.
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, 100 Blossom St., Jackson 1115, Boston, MA, 02114, USA.|Department of Orthopedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Shunan
authors.initials: S
authors.lastname: Ye
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, 100 Blossom St., Jackson 1115, Boston, MA, 02114, USA.
authors.forename: Jacson
authors.initials: J
authors.lastname: Shen
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, 100 Blossom St., Jackson 1115, Boston, MA, 02114, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.affiliation: Department of Orthopedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Cao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, 100 Blossom St., Jackson 1115, Boston, MA, 02114, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Mankin
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, 100 Blossom St., Jackson 1115, Boston, MA, 02114, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Hornicek
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, 100 Blossom St., Jackson 1115, Boston, MA, 02114, USA. zduan@mgh.harvard.edu.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics; D010597:Pharmacogenetics; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D051028:bcl-2-Associated X Protein; D017526:Receptor, IGF Type 1
keywords: Apoptosis; MDR; Osteosarcoma; p53