The expression pattern of prostaglandin E synthase and EP receptor isoforms in normal mouse skin and preinvasive skin neoplasms.
Prostaglandin (PG) E(2), the predominant PG in skin, accumulates in experimentally produced mouse skin tumors. PGE(2) induces proliferation of mouse keratinocytes in vitro, epidermal hyperplasia and dysplasia, a promoted epidermis phenotype, and angiogenesis in keratin 5 promoter (K5) cyclooxygenase (COX)-2-transgenic NMRI mouse skin in vivo. PGE(2) is synthesized by COX-catalysed oxygenation of arachidonic acid to PGH(2) and its conversion to PGE(2) by prostaglandin E synthase (PGES) isoforms. PGE(2) signals via PGE(2) receptor isoforms EP1-EP4. Here, we investigated the expression profiles of PGES and EP receptors in wild type NMRI mouse skin constitutively expressing COX-1 when compared with the hyperplastic/dysplastic skin of homozygous K5 COX-2-transgenic mice and papillomas of both genotypes, which, in addition to COX-1, overexpress COX-2. The three PGES are constitutively expressed in normal and transgenic skin independent of the COX expression status. In papillomas, the increased PGE(2) levels correlate with an increased expression of mPGES-1 and cPGES. All four EP receptors were expressed in normal and transgenic skin. Only EP3 was slightly increased in transgenic skin. In papillomas of both genotypes, the expression levels of EP1 and EP4 were low when compared with those in wild type back skin. EP2 was the predominant receptor in papillomas of wild type and transgenic mice. In papillomas of wild type mice EP3 levels were slightly elevated when compared with transgenic tumors. EP1 and EP2 were localized in basal keratinocytes, sebaceous glands and CD31-positive vessels. Thus, normal and preinvasive mouse skin express the complete protein repertoire for PGE(2) biosynthesis and signalling.
Neumann
Melanie
M
Section Eicosanoids and Tumor Development, Deutsches Krebsforschungszentrum Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Dülsner
Erik
E
Fürstenberger
Gerhard
G
Müller-Decker
Karin
K
D000818:Animals; D001483:Base Sequence; D051546:Cyclooxygenase 2 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D053569:Keratin-15; D053555:Keratin-5 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D010212:Papilloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D000071876:Prostaglandin-E Synthases; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D017931:DNA Primers; D007527:Isoenzymes; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse