A new study suggests that the protein STAT1, which negatively regulates cell growth and survival, can suppress tumor growth in squamous cell carcinoma of the head and neck (SCCHN) tumors. When the promoter region of the STAT1 gene is chemically modified by a process called promoter hypermethylation, thereby inhibiting STAT1 expression, the result can increase SCCHN tumor growth.
Researchers have suggested that dysregulation of STAT proteins could play a role in tumor formation and growth. The exact mechanism by which STAT1 gene methylation is altered in SCCHN tumors had not been determined.
Jennifer Rubin Grandis, M.D., at the University of Pittsburgh, and colleagues compared expression of STAT1 in SCCHN tumors and in tissue samples from patients without cancer. They found that STAT1 expression was lower in tumors than in normal tissue. In separate laboratory experiments, they found that SCCHN cells ceased growing and died when STAT1 expression was increased above normal levels. They also found that STAT1 expression was reduced in many of the SCCHN tumors by a process called promoter hypermethylation. When they treated cells with a drug called azacytidine, which reverses hypermethylation, STAT1 expression increased and those tumor cells became more responsive to treatment with the cancer drug cisplatin. The authors suggest that STAT1 works as a tumor suppressor for SCCHN cells, but when expression is lowered, SCCHN tumors grow.
In an accompanying editorial, Heehyoung Lee, Ph.D., and Hua Yu, Ph.D., of the Beckman Research Institute in Duarte, Calif., write, "The present study reveals a novel regulatory mechanism for STAT1 in cancer. Their data show that the STAT1 promoter is hypermethylated in SCCHN tissues and cell lines and that demethylation of the STAT1 promoter can sensitize tumor cells to chemotherapeutic agent-induced apoptosis."
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Contact: Ariel Whitworth
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Journal of the National Cancer Institute
31-Jan-2006