Interferons and cell growth control

D.V. Kalvakolanu

Greenebaum Cancer Center, Departments of Microbiology and Immunology, and Medicine, Molecular and Cellular Program, Program in Oncology, University of Maryland School of Medicine, Baltimore, USA

Offprint requests to: Dr. Dhananjaya V. Kalvakolanu, Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 W. Baltimore Street, BRB-13th floor, Baltimore, MD 21201, USA. Fax: 410-328-1397. e-mail: dkalvako@umaryland.edu

Summary. Cytokines modulate cell growth, differentiation, and immune defenses in the vertebrates. Interferons (IFNs) are a unique class of cytokines that stimulate antiviral, antitumor and antigen presentation by inducing the expression of several cellular genes. Recent studies have identified a novel gene regulatory pathway activated by IFNs, which serves as a paradigm for most cytokine signal transduction pathways. A number of genes induced by IFNs participate in cell growth regulation and apoptosis. These include novel tumor suppressor genes. Although discovered as IFN-regulated factors, deletions of these genes cause leukemias in experimental models and in human patients. Genetic approaches have identified several novel regulators of apoptosis. Studies on the mechanism of action of these growth regulatory molecules are not only useful in identifying novel targets for the development of therapeutics but also help understand the molecular basis for loss of cell growth control and resistance to IFNs. This review focuses on the functions and roles of IFN regulated factors in cell growth control and mechanisms of disruption of IFN action in cancer cells. Histol. Histopathol. 15, 523-537 (2000)

Key words: Cytokines, Signaling, Gene regulation, Apoptosis, Cancer

DOI: 10.14670/HH-15.523