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 journalArticle

33 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)9286-9293
Number of pages8
JournalCancer Research
Volume67
Issue number19
DOIs
StatePublished - Oct 1 2007

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Retinoblastoma
Nitric Oxide
Inflammation
Colonic Neoplasms
Phosphatidylinositol 3-Kinase
MAP Kinase Kinase Kinases
Retinoblastoma Protein
Guanosine
Extracellular Signal-Regulated MAP Kinases
Colitis
Mitogen-Activated Protein Kinases
Inflammatory Bowel Diseases
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ying, L., Hofseth, A. B., Browning, D. D., Nagarkatti, M., Nagarkatti, P. S., & Hofseth, L. J. (2007). Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation. Cancer Research, 67(19), 9286-9293. https://doi.org/10.1158/0008-5472.CAN-07-2238

Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation. / Ying, Lei; Hofseth, Anne B.; Browning, Darren D; Nagarkatti, Mitzi; Nagarkatti, Prakash S.; Hofseth, Lorne J.

In: Cancer Research, Vol. 67, No. 19, 01.10.2007, p. 9286-9293.

Research output: Contribution to journalArticle

Ying, L, Hofseth, AB, Browning, DD, Nagarkatti, M, Nagarkatti, PS & Hofseth, LJ 2007, 'Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation', Cancer Research, vol. 67, no. 19, pp. 9286-9293. https://doi.org/10.1158/0008-5472.CAN-07-2238
Ying, Lei ; Hofseth, Anne B. ; Browning, Darren D ; Nagarkatti, Mitzi ; Nagarkatti, Prakash S. ; Hofseth, Lorne J. / Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation. In: Cancer Research. 2007 ; Vol. 67, No. 19. pp. 9286-9293.
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