Abstract
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)hyperp hosphorylation 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.
Original language | English (US) |
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Pages (from-to) | 9286-9293 |
Number of pages | 8 |
Journal | Cancer Research |
Volume | 67 |
Issue number | 19 |
DOIs | |
State | Published - Oct 1 2007 |
ASJC Scopus subject areas
- Oncology
- Cancer Research