[Resistance to Fas-mediated apoptosis in human papillomavirus type 16-immortalized human laryngeal epithelial cells after tumorigenesis].
Apoptosis plays an important role in such biological processes as multistep carcinogenesis. Human papillomavirus type 16(HPV16)-immortalized human epithelial cell lines are, for the most part, nontumorigenic in nude mice and useful for studying mechanisms involved in multistep carcinogenesis. We previously reported that HPV16-immortalized human laryngeal epithelial cell line HLEC16 formed tumors after treatment with 4-(methyl-nitrosamine)-1-(3-pyridyl)-1-butanone, and derived one tumorigenic cell line, HLEC16T. We compared sensitivity to Fas receptor-mediated apoptosis of nontumorigenic HLEC16 and tumorigenic HLEC16T. HLEC16 and HLEC16T expressed Fas protein (Fas) but not Fas-ligand (FasL) mRNA. We applied an anti-Fas monoclonal, antibody, CH11, to HLEC16 and HLEC16T, and monitored cell death. HLEC16T was found to be significantly less sensitive to CH11-mediated cell death that HLEC16. Western blot analysis showed no significant difference in levels of apoptosis-inducing protein, Bax, between HLEC16 and HLEC16T. Levels of apoptosis-inhibiting proteins Bcl-2 and Bcl-XL increased in HLEC16T. These results suggest that the inhibition of Fas-mediated apoptosis through apoptosis-inhibiting protein overexpression may promote tumorigenicity in HLEC16T.
Department of Otolaryngology, St. Marianna University School of Medicine, Kawasaki.
T
T
Kobayashi
K
K
Tsutsumi
D
D
Kuwahara
H
H
Iwatake
T
T
Takakuwa
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D007830:Larynx / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000209:etiology*; D027383:Papillomaviridae / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor