title: The modulation of apoptosis by cyclic AMP involves Akt and epidermal growth factor receptor.
abstract: Adenosine 3',5'-cyclic monophosphate (cAMP) and transforming growth factor-beta are important regulators of many biological processes. In this study we investigated the effect and its potential mechanism of cAMP on transforming growth factor-beta1- and serum deprivation-induced apoptosis in Mv1Lu cells. Transforming growth factor-beta1 treatment or serum deprivation induces apoptotic response in Mv1Lu cells. Forskolin, a cAMP-elevating agent, or 8-Bromo-cAMP (8-B-cAMP), a cell permeable cAMP analogue, inhibited the cell proliferation and markedly enhanced apoptosis induced by transforming growth factor-beta1, but completely suppressed serum deprivation-induced apoptosis. Furthermore, forskolin decreased the Akt phosphorylation, and the inhibition of phosphatidylinositol-3 kinase by LY294002 sensitized Mv1Lu cells to transforming growth factor-beta1-induced apoptosis. In addition, forskolin treatment induced tyrosine phosphorylation of epidermal growth factor receptor. Inhibition of epidermal growth factor receptor by specific inhibitor PD153035 blocked the cAMP-mediated suppression of serum deprivation-induced apoptosis. The results indicate that cAMP exerts its opposite effects in transforming growth factor-beta1- and serum deprivation-induced apoptosis via a mechanism involving the modulation of signaling components of phosphatidylinositol-3-kinase/Akt and epidermal growth factor receptor in Mv1Lu cells.
authors.affiliation: Laboratory of molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 32 Yue-Yang Road, Shanghai 200031, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Li
authors.forename: Hehua
authors.initials: H
authors.lastname: Chen
authors.forename: Jianguo
authors.initials: J
authors.lastname: Song
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology*; D008907:Mink; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D016895:Culture Media, Serum-Free; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt