Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids
J. Clin. Invest. Stavroula Kousteni, et al. 111:1651 doi:10.1172/JCI17261 [
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Figure 4Transcriptional events mediated by Elk-1, C/EBPβ, CREB, and JNK1/AP-1 are required for the antiapoptotic effects of sex steroids. Calvaria-derived osteoblastic cells were treated with 10
–7 M actinomycin D (ActD) or 10
–7 M cycloheximide (Chx) for 7 hours (
a) or with ActD or Chx for 1 hour, followed by 1-hour treatment with 10
–8 M E
2, and then 6-hour treatment with 100 μm etoposide (Etop) (
b). Apoptosis was then assayed by trypan blue uptake. HeLa cells were transfected with a GFP targeted to the nucleus and cotransfected with the ERα or the AR and the WT or dn mutants of the indicated transcription factors (
c). After a 24-hour period, cells were treated for 1 hour with 10
–8 M E
2 or DHT followed by 6-hour treatment with etoposide (100 μM). Apoptosis was assayed by direct visualization of changes in nuclear morphology. MLO-Y4 osteocytic cells were transfected with nuclear-targeted GFP and cotransfected with the ERα or the AR and the WT or dn mutants of the indicated transcription factors (
d). After a 24-hour period, cells were treated for 1 hour with 10
-8 M E
2 followed by a 6-hour treatment with etoposide (100 μM). Apoptosis was assayed as in (
b). Bars indicate means ± SD of triplicate determinations; *
P < 0.05 versus vehicle by ANOVA.
