cfos and cjun antisense oligonucleotides block mitogenesis triggered by fibroblast growth factor-2 and ACTH in mouse Y1 adrenocortical cells

In G(0)/G(1) cell cycle-arrested mouse Y1 adrenocortical cells, short pulse s (30 min to 2 h) of fibroblast growth factor-2 (FGF2) (5 pM to 1 nM) cause d induction of cFos protein by 2 h and onset of DNA synthesis stimulation b y 8-9 h. FGF2 dose-response curves for cFos induction (percent labeled nucl ei with a specific anti-cFos antibody) and DNA synthesis stimulation (bromo deoxyuridine labeling index) were linearly correlated with a correlation co efficient of 0 . 969. Inhibition of cFos and cJun protein induction with an tisense oligodeoxynucleotides (ODNs) to cfos and cjun mRNAs blocked DNA syn thesis stimulation by FGF2. Pulses (up to 2 h) of synthetic ACTH,, (1 pM to 1 nM) and natural porcine corticotropin A (10 pg/ml to 1 mug/ml) also indu ced cFos protein and DNA synthesis in G(0)/G(1)-arrested Y1 adrenal cells. ACTH dose-response curves for cFos induction and DNA synthesis stimulation were not correlated. But cfos and/or cjun antisense ODNs blocked DNA synthe sis stimulation by ACTH. Thus, signals initiated in FGF2 and ACTH receptors appear to converge to the induction of cfos and cjun genes to trigger DNA synthesis stimulation.