title: The tumor promoting activity of the EP4 receptor for prostaglandin E2 in murine skin.
abstract: To determine whether the EP4 receptor for prostaglandin E2 (PGE2) 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.
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Simper
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Rundhaug
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Mikulec
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bowen
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Shen
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lin
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Inok
authors.initials: I
authors.lastname: Surh
authors.affiliation: The Department of Molecular Carcinogenesis, Science Park, PO Box 389, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA. Electronic address: smfischer@mdanderson.org.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fischer
mesh_terms: D000818:Animals; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D007378:Interleukins; D058309:Receptors, Prostaglandin E, EP4 Subtype; C422042:interleukin 20
keywords: EP4 receptor; Murine skin; Prostaglandin E(2); Skin tumors; Tumor promotion