Interferon Partners with the SARI Tumor Suppressor Gene To Kill Cancer Cells

Cancer researchers have identified a gene regulated by interferon beta (INF-beta) that acts a tumor suppressor by inhibiting the activity of the transcription factor AP-1. AP-1 (activator protein 1) is a transcription factor, which is a heterodimeric protein, composed of proteins belonging to the c-Fos, c-Jun, ATF, and JDP families. It regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections. AP-1 in turn controls a number of cellular processes including differentiation, proliferation, and apoptosis. AP-1 is overexpressed in more than 90% of human cancers, which makes it an obvious target for developers of new chemotherapeutic agents. The search for ways to modulate AP-1 led investigators at Virginia Commonwealth University (Richmond, USA) to scrutinize a gene called SARI (Suppressor of AP-1, Regulated by IFN). The investigators selected SARI because of its high level of expression in normal cells and its almost complete absence in cancer cells.

In their paper in the December 8, 2008, online edition of the journal the Proceedings of the [U.S.] National Academy of Sciences (PNAS), the investigators described using a viral vector to implant SARI into cancer cells. INF stimulation of the SARI-infected cancer cells then caused them to stop dividing and die.

"We have uncovered a new way by which interferon can induce anti-tumor activity," said senior author Dr. Paul B. Fisher, professor of human and molecular genetics at Virginia Commonwealth University. "The identification of SARI also provides a new potential reagent for the selective killing of tumor cells."

"The present study indicates that interferon can suppress cancer growth by inhibiting expression of a cancer-dependent transcription factor that controls genes that regulate cancer cell growth," said Dr. Fisher. "The SARI gene may provide novel and selective gene therapy applications for cancer. It could also prove amenable for inhibiting proliferative disorders that depend on AP-1 activity. AP-1 plays a key role in regulating proliferation and transformation of cancer cells."

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