title: Expression of protease activated receptor-2 related to angiogenesis in tumor advancement of uterine endometrial cancers.
abstract: Protease activated receptor-2 (PAR-2) is the second member of a novel family of G-protein coupled seven-transmembrane domain receptors. PAR-2 has been reported to be expressed in various tumors and play a vital role in the regulation of cancer cell growth. The purpose of this study was to clarify the roles of PAR-2 in the angiogenic pathway in uterine endometrial cancers. PAR-2 expression was analyzed in 61 uterine endometrial cancer and 15 normal endometrium tissue specimens. PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time RT-PCR, respectively. Microvessel counts were determined by immunohistochemistry for CD31 and factor VIII-related antigen. The localization of PAR-2 was dominant in the cancer cells of endometrial cancer tissues of all cases studied. PAR-2 histoscores highly correlated with PAR-2 mRNA levels in the same tissues (r=0.87, p<0.001). PAR-2 histoscores and mRNA levels both significantly increased in uterine endometrial cancers with clinical stages (I<II<III, p<0.001), dedifferentiation (G1<G2<G3, p<0.001) and myometrial invasion (A<B, p<0.001; B<C, p<0.05) in comparison to normal endometria. There were significant correlations between PAR-2 histoscores and mRNA levels with microvessel counts in uterine endometrial cancers. PAR-2 was upregulated during uterine endometrial cancer progression with dedifferentiation and myometrial invasion. Therefore, PAR-2 might work on tumor advancement of uterine endometrial cancers via angiogenic activity.
authors.affiliation: Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu 501-1194, Japan.
authors.forename: Israt
authors.initials: I
authors.lastname: Jahan
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Syed Mahfuzul
authors.initials: SM
authors.lastname: Alam
authors.forename: Eriko
authors.initials: E
authors.lastname: Sato
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Tamaya
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000096:biosynthesis*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D044464:Receptor, PAR-2