Role of 'platelet-type' 12-lipoxygenase in skin carcinogenesis.
Murine and human skin express an abundance of lipoxygenase isoforms whose functions are not understood. Substantial data have implicated a role for the 'platelet-type' 12-lipoxygenase (P-12LO) metabolite, 12(S)-hydroxy-eicosatetraenoic acid (12-HETE), in a variety of tumor functions. Using P-12LO deficient mice, we sought to examine the role of the P-12LO pathway in tumor initiation and progression. Two distinct genetic strains of P-12LO deficient and wild-type mice, B6/129 Sv and SENCAR, were evaluated in two-stage carcinogenesis experiments. Carcinoma incidence was significantly reduced in the P-12LO deficient mice of the B6/129 Sv background but not the SENCAR-backcrossed mice. In contrast, papilloma incidence was reduced on the SENCAR background but not in the B6/129 Sv strain mice. A separate experiment employing a complete carcinogenesis protocol failed to find any difference in papilloma or carcinoma incidence. Overall, these data suggest that the P-12LO pathway may contribute to tumor incidence and progression in two-stage, but not complete, carcinogenesis, depending on the genetic background.
Virmani
J
J
Department of Pharmacology, Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Johnson
E N
EN
Klein-Szanto
A J
AJ
Funk
C D
CD
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology*; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000201:enzymology; D005260:Female; D051379:Mice; D018632:Mice, Inbred SENCAR; D018345:Mice, Knockout; D010212:Papilloma / Q000139:chemically induced / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology*
D002273:Carcinogens; D016718:Arachidonic Acid; D015127:9,10-Dimethyl-1,2-benzanthracene; D001092:Arachidonate 12-Lipoxygenase