The growth of malignant keratinocytes depends on signaling through the PGE(2) receptor EP1.
Recent discoveries shed light on the importance of prostaglandin (PG) production in the development of skin cancer. Work by Fischer et al. demonstrates that skin tumor promotion caused by ultraviolet B radiation can be decreased by up to 89% by blocking cyclooxygenase-2 (COX-2) with the drug Celecoxib. A similar study showed that Celecoxib can decrease new tumor formation by 44% in mice that already have tumors. These studies demonstrate the importance of COX-2 and PGs in the development of squamous cell carcinoma. We have explored growth signaling in a model of skin tumor progression. Because changes in PG production have been implicated in skin carcinogenesis, we examined this pathway. We found that malignant cell lines secrete more prostaglandin E(2) (PGE(2)) than the parental cells. We observed increased expression of COX-1 and -2. We also found that these cells express the PGE(2) receptors EP1 and EP4. When the cells are grown in the presence of indomethacin, the growth rate of the malignant cells is decreased. This effect can be reversed by addition of PGE(2) or an EP1 agonist to the medium. Thus, we have shown that skin tumor cells depend in part on PGE(2) signaling through the EP1 prostanoid receptor for their in vitro growth.
Thompson
E J
EJ
Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85724, USA.
Gupta
A
A
Vielhauer
G A
GA
Regan
J W
JW
Bowden
G T
GT
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D017931:DNA Primers / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D007527:Isoenzymes; D008565:Membrane Proteins; C545636:Ptger1 protein, mouse; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone