Cfp. Lotfi et Ha. Armelin, cfos and cjun antisense oligonucleotides block mitogenesis triggered by fibroblast growth factor-2 and ACTH in mouse Y1 adrenocortical cells, J ENDOCR, 168(3), 2001, pp. 381-389
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.