Ethanol-induced inhibition of cell
proliferation is modulated by insulin-like growth factor-I receptor levels
Resnicoff M, Cui S, Coppola D, Hoek JB, Rubin R
Department of Anatomy, Pathology and Cell Biology, Jefferson
Medical College, Philadelphia, Pennsylvania, USA
Ethanol inhibits the tyrosine autophosphorylation of the insulin-like growth
factor (IGF)-I receptor, an action that correlates with the inhibition of
IGF-I-stimulated cell proliferation [J. Biol. Chem. 268:21777-21782
In the current study, the IGF-I-dependent proliferation of mouse BALB/c3T3 cells
was completely inhibited by ethanol, but the growth of BALB/c3T3 cells that
overexpress the IGF-I receptor (p6 cells) was only partially inhibited by
ethanol BALB/ c3T3 cells that simultaneously overexpress both the IGF-I receptor
and IGF-I were insensitive to growth inhibition by ethanol.
In p6 cells, increasing concentrations of IGF-I overcame the inhibition of IGF-I
receptor tyrosine autophosphorylation in the presence of ethanol.
The importance of the IGF-I receptor as a specific target for ethanol was
further investigated in C6 rat giloblastoma cells that respond mitogenically to
both epidermal growth factor (EGF) and IGF-I.
The mitogenic response of C6 cells to EGF was abrogated in cells expressing
antisense mRNA to the IGF-I receptor.
Thus, EGF action in these cells is dependent on activation of an IGF-I/IGF-I
receptor autocrine pathway.
Indeed, EGF stimulated an increase in IGF-I receptor levels by more than
Ethanol completely inhibited the proliferation of C6 cells in response to either
EGF or IGF-I.
However, ethanol did not directly interfere with EGF receptor function, because
EGF-induced cell proliferation was unaffected by ethanol when added exclusively
during a 1-hr exposure to EGF.
Ethanol did not interfere with the EGF-induced increase in IGF-I receptor
The addition of both EGF and IGF-I overcame the inhibitory action of
In conclusion, the potency of ethanol as an inhibitor of IGF-I-mediated cell
proliferation correlates with the level of IGF-I receptors.
In contrast to its effect on the IGF-I-receptor, ethanol has no direct effect on
EGF receptor activation.
PMID: 8865975 [PubMed - indexed for MEDLINE]