Apoptosis-related gene expression after hyperthermia in human tongue squamous cell carcinoma cells harboring wild-type or mutated-type p53.
Hyperthermia is useful for the treatment of human head and neck cancer, as it is relatively easy to perform thermoregulation when compared with deep organs. In this study, we focused attention on the p53 as a predictive indicator of hyperthermic cancer therapy. We used two kinds of cell lines of a human squamous cell carcinoma (SAS) with identical backgrounds of function except for the p53 protein. We assayed the heat sensitivity, frequency of apoptosis, and apoptosis-related gene expression after heat treatment using DNA array. The SAS/neo (wild-type p53; wtp53) cells were sensitive to heat, and the induction of Caspase-3 activation and apoptosis in the wtp53 cells was clearly high compared with the SAS/mp53 (mutated p53; mp53) cells. The gene expression of apoptosis suppressive-genes such as IL-12 p35 decreased in the wtp53 cells, and IL-12 R beta1 increased in the mp53 cells, though apoptosis-promotive genes of Caspase-9, CD30 and CD40 were induced p53-independently by hyperthermia. It is suggested that heat-induced apoptosis was suppressed by IL-12-related genes in the mp53 cells. These findings strongly imply that p53 status is a useful candidate for a predictive indicator of the effectiveness in hyperthermic therapy.
Yasumoto
Jun-ichi
J
Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Kirita
Tadaaki
T
Takahashi
Akihisa
A
Ohnishi
Ken
K
Imai
Yuichiro
Y
Yuki
Kazue
K
Ohnishi
Takeo
T
D017209:Apoptosis / Q000235:genetics*; D019013:CD40 Antigens / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D006979:Hyperthermia, Induced; D018664:Interleukin-12 / Q000378:metabolism; D017730:Ki-1 Antigen / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014062:Tongue Neoplasms / Q000235:genetics / Q000628:therapy*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019013:CD40 Antigens; D017730:Ki-1 Antigen; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D018664:Interleukin-12; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases