Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation.

Ying L, Hofseth AB, Browning DD, Nagarkatti M, Nagarkatti PS, Hofseth LJ

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, School of Medicine, University of South Carolina, Columbia, South Carolina 29208, USA.

Patients with chronic inflammatory bowel disease have a high risk of colon cancer. The molecules that initiate and promote colon cancer and the cancer pathways altered remain undefined. Here, using in vitro models and a mouse model of colitis, we show that nitric oxide (NO) species induce retinoblastoma protein (pRb) hyperphosphorylation and inactivation, resulting in increased proliferation through the pRb-E2F1 pathway. NO-driven pRb hyperphosphorylation occurs through soluble guanylyl cyclase/guanosine 3',5'-cyclic monophosphate signaling and is dependent on the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase MEK/ERK and phosphatidylinositol 3-kinase/AKT pathways. Our results reveal a link between NO and pRb inactivation and provide insight into molecules that can be targeted in the prevention of the inflammation-to-cancer sequence.

Published 2 October 2007 in Cancer Res, 67(19): 9286-93.
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