Induction of heat shock protein 70 inhibits NF-kappa-B in squamous cell carcinoma.

Abstract

OBJECTIVE:

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

STUDY DESIGN AND SETTING:

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.

SIGNIFICANCE:

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.

• Authors: Timothy A King, Raed Abu Ghazaleh, Steven K Juhn, George L Adams, Frank G Ondrey
• Journal: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery (Otolaryngol Head Neck Surg) Vol. 133 Issue 1 Pg. 70-9 (Jul 2005) ISSN: 0194-5998 [Print] England
• PMID: 16025056 (Publication Type: Journal Article)

Chemical References

• HSP70 Heat-Shock Proteins
• NF-kappa B

Topics

• Apoptosis (physiology)
• Carcinoma, Squamous Cell (metabolism, physiopathology)
• Cell Line, Tumor
• Cell Survival (physiology)
• HSP70 Heat-Shock Proteins (biosynthesis)
• Hot Temperature
• Humans
• Mouth Neoplasms (metabolism, physiopathology)
• NF-kappa B (metabolism)
• Stress, Physiological (physiopathology)