Prostaglandin E2 receptor subtype 2 (EP2) null mice are protected against murine lung tumorigenesis.
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.


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.


CONCLUSIONS
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.
Keith
Robert L
RL
Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Denver VA Medical Center, Denver, CO 80220, USA.
Geraci
Mark W
MW
Nana-Sinkam
S Patrick
SP
Breyer
Richard M
RM
Hudish
Tyler M
TM
Meyer
Amy M
AM
Malkinson
Alvin M
AM
Dwyer-Nield
Lori D
LD
D000818:Animals; D002084:Butylated Hydroxytoluene; D048708:Cell Growth Processes / Q000502:physiology; D005260:Female; D007962:Leukocytes / Q000276:immunology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018078:Receptors, Prostaglandin E / Q000172:deficiency* / Q000235:genetics; D058307:Receptors, Prostaglandin E, EP2 Subtype
C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D002084:Butylated Hydroxytoluene; D008748:Methylcholanthrene