BACKGROUND: Manipulating prostaglandin (PG) production modulates tumor development. Elevated PGI2 production prevents murine lung cancer, while decreasing PGE2 content protects against colon cancer. PGE2 receptor subtype 2 (EP2) -deficient mice were hypothesized to be resistant to lung tumorigenesis. MATERIALS AND METHODS: EP2 null BALB/c mice and their wild-type littermates were exposed to an initiation-promotion carcinogenesis protocol and lung tumorigenesis was examined. Chronic lung inflammation was induced to determine whether EP2 ablation influenced inflammatory cell infiltration. RESULTS: Tumor multiplicity in EP2 null mice was 34% lower than in their wild-type littermates (21.9+/-3.0 vs. 14.5+/-2.9 tumors/mouse, p<0.001). The lung tumor burden, an indicator of growth rate, also declined (57%, p<0.05). All the mice exhibited similar inflammatory cell infiltration. CONCLUSION: PGE2, acting through EP2, enhanced lung tumorigenesis through a mechanism that may be distinct from its proinflammatory activity. Thus, EP2 is a potential target for novel chemoprevention strategies.
BACKGROUND: Manipulating prostaglandin (PG) production modulates tumor development. Elevated PGI2 production prevents murinelung cancer, while decreasing PGE2 content protects against colon cancer. PGE2 receptor subtype 2 (EP2) -deficient mice were hypothesized to be resistant to lung tumorigenesis. MATERIALS AND METHODS:EP2 null BALB/c mice and their wild-type littermates were exposed to an initiation-promotion carcinogenesis protocol and lung tumorigenesis was examined. Chronic lung inflammation was induced to determine whether EP2 ablation influenced inflammatory cell infiltration. RESULTS:Tumor multiplicity in EP2 null mice was 34% lower than in their wild-type littermates (21.9+/-3.0 vs. 14.5+/-2.9 tumors/mouse, p<0.001). The lung tumor burden, an indicator of growth rate, also declined (57%, p<0.05). All the mice exhibited similar inflammatory cell infiltration. CONCLUSION:PGE2, acting through EP2, enhanced lung tumorigenesis through a mechanism that may be distinct from its proinflammatory activity. Thus, EP2 is a potential target for novel chemoprevention strategies.
Authors: Katelyn J Siegrist; DeeDee Romo; Brad L Upham; Michael Armstrong; Kevin Quinn; Lauren Vanderlinden; Ross S Osgood; Kalpana Velmurugan; Marc Elie; Jonathan Manke; Dominik Reinhold; Nichole Reisdorph; Laura Saba; Alison K Bauer Journal: Toxicol Sci Date: 2019-05-01 Impact factor: 4.849
Authors: Lori Dwyer-Nield; Gregory A Hickey; Micah Friedman; Kevin Choo; Debbie G McArthur; Meredith A Tennis; Melissa L New; Mark Geraci; Robert L Keith Journal: Cancer Prev Res (Phila) Date: 2017-08-29
Authors: Terry W Moody; Christopher Switzer; Wilmarie Santana-Flores; Lisa A Ridnour; Marc Berna; Michelle Thill; Robert T Jensen; Anna Sparatore; Piero Del Soldato; Grace C Yeh; David D Roberts; Giuseppe Giaccone; David A Wink Journal: Lung Cancer Date: 2009-07-23 Impact factor: 5.705
Authors: Carolyn J Baglole; Sanjay B Maggirwar; Thomas A Gasiewicz; Thomas H Thatcher; Richard P Phipps; Patricia J Sime Journal: J Biol Chem Date: 2008-08-12 Impact factor: 5.157
Authors: Melissa L New; Collin M White; Polly McGonigle; Debbie G McArthur; Lori D Dwyer-Nield; Daniel T Merrick; Robert L Keith; Meredith A Tennis Journal: Cancer Prev Res (Phila) Date: 2018-07-25