Activin A inhibits cell-cycle progression induced by insulin-like growth factor-I in Balb/c 3T3 cells.
The present study was carried out to examine the effect of activin A on cell-cycle progression induced by insulin-like growth factor-I (IGF-I) in Balb/c 3T3 cells. When activin A was added together with IGF-I to competent cells primed with epidermal growth factor (primed competent cells), both [3H]thymidine incorporation and nuclear labelling induced by IGF-I were inhibited. The inhibition was concentration-dependent and the maximum inhibition was obtained with 1 nmol activin A/1. To ascertain the time in which activin A exerted its inhibitory action, we divided 12 h, the time required for primed competent cells to progress towards the S phase, into four periods and activin A was added during each of the four periods. It was effective when added during either the second (3 to 6 h) or the third period (6 to 9 h) but it did not affect cell-cycle progression when added during the first (0 to 3 h) or the last period (9 to 12 h). We then examined whether activin A affected intracellular events elicited by IGF-I. It did not affect either autophosphorylation of the IGF-I receptor or calcium entry induced by IGF-I. Likewise, it did not cause any change in the radioactivity of 1,2-diacylglycerol (DAG) in cells prelabelled with [3H]myristate while the increase in the mass of DAG induced by IGF-I was markedly reduced by activin A. The dose-response relationship for the activin A-mediated reduction of DAG mass correlated well with th at for the activin A-mediated reduction of DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
I
I
Kojima
H
H
Mogami
N
N
Kawamura
H
H
Shibata
D016475:3T3 Cells; D028341:Activins; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D004075:Diglycerides / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D007265:Inhibins / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation
C011439:1,2-diacylglycerol; D004075:Diglycerides; D006133:Growth Substances; D028341:Activins; D007265:Inhibins; D007334:Insulin-Like Growth Factor I; D002118:Calcium