Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation

Lei Ying, Anne B. Hofseth, Darren D. Browning, Mitzi Nagarkatti, Prakash S. Nagarkatti, Lorne J. Hofseth

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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 languageEnglish (US)
Pages (from-to)9286-9293
Number of pages8
JournalCancer Research
Issue number19
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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