Induction of heat shock protein 70 inhibits NF-kappa-B in squamous cell carcinoma.
OBJECTIVE
To determine the relationship between heat shock proteins (HSPs) and the proinflammatory, anti-apoptosis mediator NF-kappa-B in squamous cell carcinoma.


METHODS
CA-9-22 cells were exposed to heat stress to induce the production of HSPs. Immunoblot and reporter gene experiments determined the inducibility of HSP production and the activation of cytokine-induced NF-kappa-B. Immunoblot experiments determined the presence of the inhibitor-kappa-B-alpha (IkappaB alpha).


RESULTS
CA-9-22 cells can be induced by heat stress to produce HSPs at 100-fold above baseline levels. The induction of HSPs prevents the activation and nuclear translocation of NF-kappa-B despite stimulation with IL-1beta and TNF-alpha.


CONCLUSIONS
Constitutive activation of NF-kappa-B is prevented by HSP induction through an increase in IkappaB alpha synthesis.


CONCLUSIONS
The induction of HSP70 alters the inflammatory milieu associated with squamous cell carcinoma progression through the inhibition of NF-kappa-B and may ultimately promote apoptosis in head and neck carcinoma.
King
Timothy A
TA
Department of Otorhinolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis 55455, USA.
Ghazaleh
Raed Abu
RA
Juhn
Steven K
SK
Adams
George L
GL
Ondrey
Frank G
FG
D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism*; D013312:Stress, Physiological / Q000503:physiopathology
D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B