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Publication : Loss of cannabinoid receptor 1 accelerates intestinal tumor growth.

First Author  Wang D Year  2008
Journal  Cancer Res Volume  68
Issue  15 Pages  6468-76
PubMed ID  18676872 Mgi Jnum  J:140031
Mgi Id  MGI:3811660 Doi  10.1158/0008-5472.CAN-08-0896
Citation  Wang D, et al. (2008) Loss of cannabinoid receptor 1 accelerates intestinal tumor growth. Cancer Res 68(15):6468-76
abstractText  Although endocannabinoid signaling is important for certain aspects of gastrointestinal homeostasis, the role of the cannabinoid receptors (CB) in colorectal cancer has not been defined. Here we show that CB1 expression was silenced in human colorectal cancer due to methylation of the CB1 promoter. Our genetic and pharmacologic studies reveal that loss or inhibition of CB1 accelerated intestinal adenoma growth in Apc(Min/+) mice whereas activation of CB1 attenuated intestinal tumor growth by inducing cell death via down-regulation of the antiapoptotic factor survivin. This down-regulation of survivin by CB1 is mediated by a cyclic AMP-dependent protein kinase A signaling pathway. These results indicate that the endogenous cannabinoid system may represent a potential therapeutic target for prevention or treatment of colorectal cancer.
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