Open AccessThe tumor promoting activity of the EP4 receptor for prostaglandin E 2 in murine skin
Author(s) -
Simper Melissa S.,
Rundhaug Joyce E.,
Mikulec Carol,
Bowen Rebecca,
Shen Jianjun,
Lu Yue,
Lin Kevin,
Surh Inok,
Fischer Susan M.
Publication year - 2014
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2014.06.013
Subject(s) - prostaglandin e2 receptor , prostaglandin e , prostaglandin e2 , receptor , skin tumor , prostaglandin , pharmacology , chemistry , medicine , endocrinology , cancer research , biology , microbiology and biotechnology , agonist , cancer , carcinogenesis
To determine whether the EP4 receptor for prostaglandin E 2 (PGE 2 ) contributes to the tumor promoting activity of PGs in murine skin, EP4 over‐expressing mice (BK5.EP4) were generated and subjected carcinogenesis protocols. An initiation/promotion protocol resulted in 25‐fold more squamous cell carcinomas (SCCs) in the BK5.EP4 mice than wild type (WT) mice. An increase in SCCs also occurred following treatment with initiator alone or UV irradiation. The initiator dimethylbenz[a]anthracene caused cytotoxicity in BK5.EP4, but not WT mice, characterized by sloughing of the interfollicular epidermis, regeneration and subsequent SCC development. A comparison of transcriptomes between BK5.EP4 and WT mice treated with PGE2 showed a significant upregulation of a number of genes known to be associated with tumor development, supporting a pro‐tumorigenic role for the EP4 receptor.