Y. Umayahara et al., ESTROGEN REGULATION OF THE INSULIN-LIKE GROWTH-FACTOR-I GENE-TRANSCRIPTION INVOLVES AN AP-1 ENHANCER, The Journal of biological chemistry, 269(23), 1994, pp. 16433-16442
As a step toward elucidating the physiological role of insulin-like gr
owth factor-I (IGF-I) in mediating estrogen action, we sought to deter
mine the molecular basis of the phenomenon. In HepG2 cells expressing
exogenous estrogen receptors (ER), a reporter gene plasmid containing
600 base pairs of the chicken IGF-I promoter enhanced expression of lu
ciferase 8.6-fold in response to 10(-6) M 17 beta-estradiol, indicatin
g that the IGF-I promoter is a target of estrogen regulation. Although
no conventional estrogen-responsive element was identified within the
promoter fragment, the AP-1 motif located therein was shown to be ess
ential; the estrogen-responsive enhancement of the Fos-Jun binding to
the AP-1 motif, which takes place by means of post-translational modif
ication, mediates the estrogen action. A direct or indirect interactio
n between the estrogen-ER complex and the Fos-Jun complex seems to fac
ilitate the Fos-Jun binding to the target DNA. Although ER binding to
the target DNA was not considered to be involved in the signaling path
way, the DNA binding domain-deficient ER did not mediate the phenomeno
n, providing support for the existence of a unique function of the DNA
binding domain of ER in facilitating some protein-protein interaction
. In conclusion, our present observations demonstrate that the chicken
IGF-I gene promoter is controlled by estrogen through a unique pathwa
y involving Fos, Jun, and the DNA binding domain of ER.