Abstract
Breast cancer is known to be a hormone-dependent disease, and estrogens through an interaction with estrogen receptor (ER) enhance the proliferative and metastatic activity of breast tumor cells. Here we show a critical role of transactivation of BIG3, brefeldin A-inhibited guanine nucleotide-exchange protein 3, in activation of the estrogen/ER signaling in breast cancer cells. Knocking-down of BIG3 expression with small-interfering RNA (siRNA) drastically suppressed the growth of breast cancer cells. Subsequent co-immunoprecipitation and immunoblotting assays revealed an interaction of BIG3 with prohibitin 2/repressor of estrogen receptor activity (PHB2/REA). When BIG3 was absent, stimulation of estradiol caused the translocation of PHB2/REA to the nucleus, enhanced the interaction of PHB2/REA and ER[alpha], and resulted in suppression of the ER[alpha]; transcriptional activity. On the other hand, when BIG3 was present, BIG3 trapped PHB2/REA in cytoplasm and inhibited its nuclear translocation, and caused enhancement of ER[alpha]; transcriptional activity. Our results imply that BIG3 overexpression is one of the important mechanisms causing the activation of the estrogen/ER[alpha]; signaling pathway in the hormone-related growth of breast cancer cells.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, JW., Akiyama, M., Park, JH. et al. Activation of an Estrogen/ Estrogen Receptor Signaling by BIG3 Through Its Inhibitory Effect on Nuclear Transport of PHB2/REA in Breast Cancer. Nat Prec (2009). https://doi.org/10.1038/npre.2009.2834.1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/npre.2009.2834.1