Does diethylstilbestrol (DES) change the stress fiber organization in C6 rat glioma cells?
C6 Rat glioma cells acquire an astrocyte-like morphology (cytoplasmic shrinking) after exposure to beta-adrenergic compounds (e.g., isoproterenol) in serum-free medium. This morphological response is mediated by elevation of the intracellular cAMP level and possibly by activation of a kinase phosphorylating and inactivating the myosin-L-kinase in analogy to observations with smooth muscle cells. The result is a disturbance of the stress fiber function, which depends on a cooperation between actin and myosin. Diethylstilbestrol (DES) induces an identical morphological response in these cells under serum-free conditions. However, under the influence of DES no increase of the cAMP level was observed. In addition, at concentrations not inducing these morphological responses, DES inhibits the isoproterenol-induced effect when administered simultaneously or prior to the beta-receptor agonist. DES does not inhibit the isoproterenol-mediated morphological response when added after isoproterenol treatment. Furthermore, if serum is added to cells showing the isoproterenol- or DES-mediated astrocyte-like morphology (DES or isoproterenol present all the time) the cells regain their normal fibroblast-like morphology within 30 min. In view of these results the question arises whether DES interferes with myosin-L-chain phosphorylation or whether it directly interacts with the cytoskeleton stress fiber components, as cytochalasin B1 does. Thus it remains to be established whether the observed effects are related to the estrogenic activity of DES. Similar effects were observed with Syrian hamster embryo fibroblasts under the influence of DES and the naturally occurring steroid estrogen 17-beta-estradiol.
Schiffmann
D
D
Institute of Toxicology, University of Würzburg, Federal Republic of Germany.
Tas
P
P
Koschel
K
K
D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D003599:Cytoskeleton / Q000187:drug effects*; D004054:Diethylstilbestrol / Q000633:toxicity*; D005910:Glioma / Q000473:pathology*; D007545:Isoproterenol / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D004054:Diethylstilbestrol; D000242:Cyclic AMP; D007545:Isoproterenol