title: Epidermal growth factor modulates claudins and tight junctional functions in ovarian cancer cell lines.
abstract: Ovarian adenocarcinomas, like human ovarian surface epithelial cells, form functional tight junctions. Tight junction molecules claudin-3 and claudin-4, which are the receptors of Clostridium perfringens enterotoxin (CPE), are abnormally upregulated in epithelial ovarian cancers of all subtypes including, mucinous cystadenocarcinoma and serous cystadenocarcinoma. Clostridium perfringens enterotoxin may be a novel tumor-targeted therapy for ovarian cancers. In epithelial ovarian cancers, overexpression of epidermal growth factor receptor has been observed and the exogenous ligand EGF induces epithelial-mesenchymal transition in ovarian surface epithelium. Epidermal growth factor (EGF) signaling modulates expression of claudins with changes of fence and barrier functions in various cell types. However, the regulation of tight junctions by EGF in ovarian cancers remains unclear. In the present study, to investigate the mechanisms of the regulation of tight junctions in ovarian cancers, ovarian cancer cell lines mucinous cystadenocarcinoma (MCAS) and serous cystadenocarcinoma (HUOA) were treated with EGF. Epidermal growth factor downregulated claudin-3 in MCAS and claudin-4 in HUOA by inducing degradation of the proteins with changes in structures and functions of tight junctions via the MEK/ERK or PI3K/Akt signaling pathway. In addition, in HUOA but not MCAS, EGF downregulated the cytotoxic effect of CPE via claudin-4. Thus, there were different mechanisms for regulation of claudins by EGF between subtypes of epithelial ovarian cancer cells in vitro. These results indicate that EGF may affect claudins and tight junctional functions in ovarian cancer cells during cancer progression.
authors.affiliation: Department of Gynecology and Obstetrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Marie
authors.initials: M
authors.lastname: Ogawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Someya
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nomura
authors.forename: Akira
authors.initials: A
authors.lastname: Takasawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
mesh_terms: D045744:Cell Line, Tumor; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism; D062465:Claudin-3 / Q000235:genetics / Q000378:metabolism; D062506:Claudin-4 / Q000235:genetics / Q000378:metabolism; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D019108:Tight Junctions / Q000502:physiology*
chemical_list: D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor