Defective heat shock factor 1 inhibits the growth of fibrosarcoma derived from simian virus 40/T antigen‑transformed MEF cells.
Heat shock factor 1 (Hsf1) serves an important role in regulating the proliferation of human tumor cell lines in vitro and tissue specific tumorigenesis in certain mouse models. However, its role in viral‑oncogenesis remains to be fully elucidated. In the current study, the role of Hsf1 in fibroblastoma derived from simian virus 40/T antigen (SV40/TAG)‑transformed mouse embryonic fibroblast (MEF) cell lines was investigated. Knockout of Hsf1 inhibited MEF cell proliferation in vitro and fibroblastoma growth and metastasis to the lungs in vivo in nude mice. Knockout of Hsf1 increased the protein expression levels of p53 and phosphorylated retinoblastoma protein (pRb), however reduced the expression of heat shock protein 25 (Hsp25) in addition to the expression of the angiogenesis markers vascular endothelial growth factor, cluster of differentiation 34 and factor VIII related antigen. Furthermore, immunoprecipitation indicated that knockout of Hsf1 inhibited the association between SV40/TAG and p53 or pRb. These data suggest that Hsf1 is involved in the regulation of SV40/TAG‑derived fibroblastoma growth and metastasis by modulating the association between SV40/TAG and tumor suppressor p53 and pRb. The current study provides further evidence that Hsf1 may be a novel therapeutic target in the treatment of cancer.
Henan Key Laboratory of Engineering Antibody Medicine, Henan International Union Laboratory of Antibody Medicine and Chaperone, Henan University School of Medicine, Kaifeng, Henan 475004, P.R. China.
Qiying
Q
Jiang
Henan Key Laboratory of Engineering Antibody Medicine, Henan International Union Laboratory of Antibody Medicine and Chaperone, Henan University School of Medicine, Kaifeng, Henan 475004, P.R. China.
Zhi
Z
Zhang
Henan Key Laboratory of Engineering Antibody Medicine, Henan International Union Laboratory of Antibody Medicine and Chaperone, Henan University School of Medicine, Kaifeng, Henan 475004, P.R. China.
Shulian
S
Li
Henan Key Laboratory of Engineering Antibody Medicine, Henan International Union Laboratory of Antibody Medicine and Chaperone, Henan University School of Medicine, Kaifeng, Henan 475004, P.R. China.
Zhaoyang
Z
Wang
Henan Key Laboratory of Engineering Antibody Medicine, Henan International Union Laboratory of Antibody Medicine and Chaperone, Henan University School of Medicine, Kaifeng, Henan 475004, P.R. China.
Yuanfang
Y
Ma
Henan Key Laboratory of Engineering Antibody Medicine, Henan International Union Laboratory of Antibody Medicine and Chaperone, Henan University School of Medicine, Kaifeng, Henan 475004, P.R. China.
Yanzhong
Y
Hu
D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D000957:Antigens, Viral, Tumor / Q000235:genetics* / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005354:Fibrosarcoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary / Q000821:virology; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013539:Simian virus 40 / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
D018952:Antigens, CD34; D000957:Antigens, Viral, Tumor; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; C490017:Hsf1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D014841:von Willebrand Factor