Enhanced apoptosis under low serum conditions in human glioblastoma cells by connexin 43 (Cx43).
Connexin 43 (Cx43), a structural component of gap junctions, is believed to function as a tumor suppressor gene. Previously, we showed that expression of Cx43 suppresses cell proliferation and tumorigenicity of human glioblastoma cells [Huang et al., Cancer Res 58:5089-5096, 1998] and enhances apoptosis in response to chemotherapeutic agents [Huang et al., Int J Cancer 92:130-138, 2001]. In the present study, we demonstrated that expression of Cx43 in human glioblastoma cells potentiated an apoptotic program under low-serum conditions. The Cx43-mediated effect was coupled with a decreased expression of the specific apoptosis-inhibitor bcl-2. Overexpression of bcl-2 in Cx43-transfected cells conferred resistance to apoptosis induced under low-serum conditions, suggesting that the Cx43-mediated apoptosis under low-serum conditions is regulated, in part, through the downregulation of bcl-2 expression. Furthermore, application of the phosphatidylinositol-3'-OH kinase inhibitor LY294002 specifically induced apoptosis in Cx43-transfected cells. Our results demonstrate a new role of Cx43 in the mediation of apoptosis under low serum conditions.
Huang
R
R
Division of Research, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Liu
Y G
YG
Lin
Y
Y
Fan
Y
Y
Boynton
A
A
Yang
D
D
Huang
R P
RP
D017209:Apoptosis / Q000235:genetics*; D002867:Chromones / Q000494:pharmacology; D018031:Connexin 43 / Q000235:genetics*; D003470:Culture Media; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014407:Tumor Cells, Cultured
D002867:Chromones; D018031:Connexin 43; D003470:Culture Media; D004968:Estrogens, Non-Steroidal; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one