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COX-2 levels are elevated in smokers

PHILADELPHIA -- Tobacco smoke triggers the production of COX-2, a cellular protein linked to the development and progression of cancer, according to research published in the January 15 issue of the journal Cancer Research.

Tobacco smoke also promoted rapid cellular production of two proteins that initiate an epidermal growth factor receptor (EGFR) driven cascade leading to the production of COX-2, the report stated.

The report by Andrew J. Dannenberg, M.D., director of cancer prevention, Weill Medical College of Cornell University, and colleagues, indicates that smokers produce as much as four times the amount of COX-2 in oral mucosal cells lining their mouths than their non-smoking counterparts.

After observing the increased amount of COX-2 in the oral mucosa of smokers, Dannenberg and his team of collaborating scientists exposed cells in culture to tobacco smoke to define the mechanism underlying smoke-induced elevation of COX-2.

The researchers determined that COX-2 levels were increased due to tobacco smoke induced activation of EGFR, a cell membrane protein also associated with various types of cancer. Tobacco smoke stimulated the oral mucosal cells to rapidly release two proteins that activate the EGFR, initiating a cascade resulting in COX-2 protein production.

"In an oral mucosal cell line, tobacco smoke clearly activated the epidermal growth factor receptor. Tobacco smoke caused increased EGFR phosphorylation leading to increased COX-2 production," Dannenberg reported.

"We were able to block the induction of COX-2 with either a small molecule that inhibited EGFR activity or an antibody that prevented ligands from binding to and activating the EGFR. These findings led us to question whether tobacco smoke initiated the process of increasing COX-2 production by first stimulating production of proteins that controlled activity of the EGF receptor," Dannenberg said.

Cells exposed to tobacco smo
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Contact: Russell Vanderboom, Ph.D
vanderboom@aacr.org
215-440-9300
American Association for Cancer Research
15-Jan-2005


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