Effect of endothelin-1 as growth factor on a human glioma cell line; its characteristic promotion of DNA synthesis.
In addition to its powerful vasoconstrictive activity, endothelin-1 (ET-1) has been recognized to stimulate DNA synthesis in some cell lines. In this study, we confirmed the existence of ET-1 receptor in YKG-1 human glioma cells, and investigated its effect on DNA synthesis in YKG-1 for 6 consecutive days, comparing it with that of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I). Scatchard analysis of the binding data revealed the presence of a single class of high-affinity binding molecule. The apparent dissociation constant (Kd) was 5.2 x 10(-9) M and the maximal binding capacity (B max) was 4.7 x 10(4) sites/cell. The percentage of non-cycling cells was initially more than 85%, and decreased to 55.40%, 24.22%, 11.50%, and 7.51% on days 1, 2, 4, and 6, respectively, after ET-1 stimulation. Although ET-1 reduces the fraction of non-cycling cells more slowly than other growth factors such as EGF, PDGF and IGF-I, it reaches the same level as the others by day 6. These results indicate that YKG-1 human glioma cells have ET-1 receptors and that ET-1 initiates a peculiar slow induction of DNA synthesis in these cells, suggesting that secondary factors might exist to accelerate the DNA synthesis in response to ET-1.
Asano
T
T
Department of Neurosurgery, Tokyo Medical and Dental University, School of Medicine, Japan.
Aoyagi
M
M
Hirakawa
K
K
Ikawa
Y
Y
D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005910:Glioma; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D016232:Endothelins; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D017466:Receptors, Endothelin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I