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

Abstract

In G(0)/G(1) cell cycle-arrested mouse Y1 adrenocortical cells, short pulses (30 min to 2 h) of fibroblast growth factor-2 (FGF2) (5 pM to 1 nM) caused induction of cFos protein by 2 h and onset of DNA synthesis stimulation by 8-9 h. FGF2 dose-response curves for cFos induction (percent labeled nuclei with a specific anti-cFos antibody) and DNA synthesis stimulation (bromodeoxyuridine labeling index) were linearly correlated with a correlation coefficient of 0.969. Inhibition of cFos and cJun protein induction with antisense oligodeoxynucleotides (ODNs) to cfos and cjun mRNAs blocked DNA synthesis stimulation by FGF2. Pulses (up to 2 h) of synthetic ACTH(39) (1 pM to 1 nM) and natural porcine corticotropin A (10 pg/ml to 1 microg/ml) also induced 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 synthesis 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.