Role of 'platelet-type' 12-lipoxygenase in skin carcinogenesis

Cancer Lett. 2001 Jan 26;162(2):161-5. doi: 10.1016/s0304-3835(00)00634-0.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Arachidonate 12-Lipoxygenase / deficiency
  • Arachidonate 12-Lipoxygenase / genetics
  • Arachidonate 12-Lipoxygenase / physiology*
  • Arachidonic Acid / metabolism
  • Blood Platelets / enzymology*
  • Carcinogens
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / enzymology
  • Female
  • Mice
  • Mice, Inbred SENCAR
  • Mice, Knockout
  • Papilloma / chemically induced
  • Papilloma / enzymology
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / enzymology*

Substances

  • Carcinogens
  • Arachidonic Acid
  • 9,10-Dimethyl-1,2-benzanthracene
  • Arachidonate 12-Lipoxygenase