title: Evaluation of the chemosensitivity of head and neck cancer cells based on the diverse function of mutated-p53.
abstract: Pre-therapeutic evaluation of p53 gene is very important for treating patients with head and neck cancer. However, the analysis for p53 gene has generally been done by immunohistochemistry, polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and direct sequencing. Functional analysis system for p53 transcriptional activity in mammalian cells is now required. We developed a functional analysis system for p53 transcriptional activity in cancer cells. We used two human head and neck cancer cell lines harboring mutated p53 gene, HSG (Asn30Ser) and TYS (Asp281His), and a human osteosarcoma cell line, Saos-2 as a control. We transfected these cells with luciferase reporter plasmids containing promoter sequence of p53 target genes (p21waf1, BAX, MDM2, p53AIP1 or PUMA). After treating the cells with chemotherapeutic drugs, alteration of the luciferase activity was measured. In HSG cells, none of the target gene promoters was activated by treatment with chemotherapeutic drugs. In TYS cells, p21waf1 promoter was markedly activated by treatment with chemotherapeutic drugs, but Bax and p53AIP1 promoter was not activated. This type of mutated-p53 in TYS cells prevents cell death from DNA damage, and probably accumulates genetic alterations and accelerates the malignant progression of the cells by DNA damaging therapy. Thus, analysis for the diverse function of mutated-p53 may help to determine the therapeutic strategy, especially for chemotherapy and radiation in the individual patients with head and neck cancer.
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi 321-0293, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shinagawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kawamata
authors.forename: Fumie
authors.initials: F
authors.lastname: Omotehara
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Nakashiro
authors.forename: Mohammad O
authors.initials: MO
authors.lastname: Hoque
authors.forename: Tadashi
authors.initials: T
authors.lastname: Furihata
authors.forename: Hideki
authors.initials: H
authors.lastname: Horiuchi
authors.forename: Yataka
authors.initials: Y
authors.lastname: Imai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimori
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujibayashi
mesh_terms: D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003062:Codon / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D017930:Genes, Reporter; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000096:biosynthesis; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins; D017354:Point Mutation; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C438378:BBC3 protein, human; C493956:CDKN1A protein, human; D003062:Codon; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C414742:P53AIP1 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D008156:Luciferases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2