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Fox Chase Researchers Find Estrogen May Help Precancerous Cells Spread in Oral Cavity

PHILADELPHIA (January 4, 2011) – Head and neck cancer is the sixth most common type of cancer and is on the rise in some demographic groups, including young women without any known risk factors. Now, researchers at Fox Chase Cancer Center report that estrogen may increase the movement of precancerous cells in the mouth and thus promote the spread of the disease within the oral cavity. The new results, which are reported in the January issue of Cancer Prevention Research, may lead to novel chemoprevention strategies in the future.

Margie Clapper, PhD, Co-leader of the Cancer Prevention and Control Program at Fox Chase Cancer Center, and colleagues reported earlier this year that estrogen metabolism changes after smoke exposure in the lungs and may contribute to lung cancer. To find out if this female hormone influences development of head and neck cancer, Ekaterina Shatalova, PhD, a postdoctoral fellow and first author on the paper, examined the impact of estrogen on precancerous and cancerous cells.

They found that estrogen induces the expression of an enzyme called cytochrome P450 1B1 (CYP1B1), which is responsible for breaking down toxins and metabolizing estrogen. Interestingly, CYP1B1 induction occurred only in precancerous cells, which are neither totally normal or cancerous. Interestingly, estrogen did not induce CYP1B1 in cancer cells.

With closer investigation, the team found that depleting the expression of CYP1B1 diminished the ability of precancerous cells to move and divide, as compared to similar cells with normal levels of CYP1B1.  Estrogen also reduced cell death in the precancerous cells, irrespective of the amount of CYP1B1 present.

 “In the future we would like to find a natural or dietary agent to deplete the CYP1B1 enzyme and see if we can prevent oral cancer at the precancerous stage,” said Shatalova.

“Our previous studies showed that the CYP1B1 enzyme sits at the hub of changes that occur in the lungs after smoke exposure.   We were now able to look at its role in a more direct fashion by removing it from precancerous cells of the oral cavity,” Clapper says. “We found that cells lacking it move slower.  CYP1B1 could be a wonderful target in precancerous lesions of the head and neck, because by attacking it, we might stop these lesions from progressing or moving to a more advanced stage.”  In addition, patients diagnosed with head and neck cancer are at a high risk of developing a second primary tumor, which is associated with poorer overall survival. Finding a way to reduce these subsequent tumors could improve patients’ survival.

Co-authors on the study include Andres J.P. Klein-Szanto, Karthik Devarajan, and Edna Cukierman, all of whom are at Fox Chase Cancer Center.

Clapper’s study on estrogen and lung cancer appeared in the June 3, 2010 issue of Cancer Prevention Research.

Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach.  For more information, call 1-888-FOX CHASE or (1-888-369-2427).

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