RRC ID 76432
著者 Terauchi M, Kajiyama H, Shibata K, Ino K, Mizutani S, Kikkawa F.
タイトル Anti-progressive effect of neutral endopeptidase 24.11 (NEP/CD10) on cervical carcinoma in vitro and in vivo.
ジャーナル Oncology
Abstract OBJECTIVES:Neutral endopeptidase 24.11 (NEP) is known to play important roles in the maintenance of homeostasis or in neoplastic transformation and tumor progression in certain human malignancies through the enzymatic inactivation of bioactive peptides such as endothelin-1 (ET-1), angiotensin-II, and bombesin.
METHODS:In this study, we first investigated NEP expression in cervical carcinoma by immunohistochemical staining and Western blot analysis. Next, we examined NEP functions in vitro and in vivo by generating NEP-overexpressing cervical carcinoma cells.
RESULTS:We found a significant decrease in cellular proliferative and invasive abilities with a reduced ET-1 concentration in the conditioned medium by NEP overexpression in cervical carcinoma CaSki cells, which have an ET-1 autocrine loop. In addition, these potentials were cancelled by blockade of NEP activity with a specific inhibitor. Although vector-transfected CaSki cells could grow even in serum-free media, NEP-overexpressing cells failed to proliferate in these media. Furthermore, we demonstrated that NEP suppressed tumor formation of subcutaneous xenografts using nude mice.
CONCLUSIONS:Our results indicated that NEP functions as a tumor-suppressor gene in cervical carcinoma cells, and its expression may have prognostic significance. Further elucidation of the mechanism underlying the observed effect of NEP will contribute to a better understanding of its role in the pathophysiology of cervical carcinoma.
巻・号 69(1)
ページ 52-62
公開日 2005-1-1
DOI 10.1159/000087476
PII 87476
PMID 16103735
MeSH Animals Antineoplastic Agents / pharmacology* Blotting, Western Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Disease Progression Female Flow Cytometry Humans Immunohistochemistry Mice Mice, Nude Neprilysin / pharmacology* Plasmids Time Factors Transfection Uterine Cervical Neoplasms / drug therapy* Uterine Cervical Neoplasms / pathology
IF 2.642
リソース情報
ヒト・動物細胞 TCS(RCB0638)