title: EGF-Induced Connexin43 Negatively Regulates Cell Proliferation in Human Ovarian Cancer.
abstract: Connexin43 (Cx43) has been shown to regulate cell proliferation and its downregulation is correlated with poor prognosis and survival in several types of human cancer. Cx43 expression levels are frequently downregulated in human ovarian cancer, suggesting a potential role for Cx43 in regulating the progression of this disease. Epidermal growth factor (EGF) is a well-characterized hormone that stimulates ovarian cancer cell proliferation. Although EGF is able to regulate Cx43 expression in other cell types, it is unclear whether EGF can regulate Cx43 expression in ovarian cancer cells. Additionally, it remains unknown whether Cx43 is involved in EGF-stimulated ovarian cancer cell proliferation. In the present study, we demonstrate that treatment with EGF upregulates Cx43 expression in two ovarian cancer cell lines, SKOV3 and OVCAR4. Although treatment with EGF activates both ERK1/2 and Akt signaling pathways, pharmacological inhibition and siRNA-mediated knockdown suggest that only the activation of Akt1 is required for EGF-induced Cx43 upregulation. Functionally, Cx43 knockdown enhanced basal and EGF-induced cell proliferation, whereas the proliferative effects of EGF were reduced by Cx43 overexpression. Co-treatment with the gap junction inhibitor carbenoxolone did not alter the suppressive effects of Cx43 overexpression on EGF-induced cell proliferation, suggesting a gap junction-independent mechanism. This study reveals an important role for Cx43 as a negative regulator of EGF-induced human ovarian cancer cell proliferation.
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Xin
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jung-Chien
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Klausen
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hsun-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Qianlan
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
mesh_terms: D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018031:Connexin 43 / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; D004815:Epidermal Growth Factor