Hormone‐regulated v‐rel estrogen receptor fusion protein: reversible induction of cell transformation and cellular gene expression.

Autor: Boehmelt, G., Walker, A., Kabrun, N., Mellitzer, G., Beug, H., Zenke, M., Enrietto, P.J.
Zdroj: The EMBO Journal; December 1992, Vol. 11 Issue: 12 p4641-4652, 12p
Abstrakt: We describe the construction of a v‐rel estrogen receptor fusion protein (v‐relER) which allows the regulation of v‐rel oncoprotein activity by hormone. In the presence of estrogen, v‐relER readily transformed primary chicken fibroblasts and bone marrow cells in vitro. In both cell types, v‐rel‐specific transformation was critically dependent on the presence of estrogen or the estrogen agonist 4‐hydroxytamoxifen (OHT). Withdrawal of estrogen or application of an estrogen antagonist, ICI164,384 (ICI) caused a reversal of the transformed phenotype. We also demonstrate that the v‐relER protein binds to NF‐kappa B sites in an estrogen‐dependent manner, thereby showing that sequence‐specific DNA binding of v‐relER is critical for the activation of its transforming capacity. In transient transfection experiments, we failed to demonstrate a clear repressor or activator function of the v‐rel moiety in v‐relER. However, in v‐relER‐transformed bone marrow cells, estrogen and OHT induced elevated mRNA levels of two cellular genes whose expression is constitutive and high in v‐rel‐transformed cells. These results suggest that v‐rel might exert part of its activity as an activator of rel‐responsive genes.
Databáze: Supplemental Index