Oncology Medical News about bbreast cancer;nuclear of PHB2/REA;BIG3;activation of an estrogen/estrogen receptor signaling

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Activation of an estrogen/estrogen receptor signaling by BIG3 through its inhibitory effect on nuclear transport of PHB2/REA in breast cancer
Cancer Science, 06/05/09

Kim JW et al. - In a trial to assess the role of transactivation of brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) in activation of the estrogen/estrogen receptor (ER) signaling in breast cancer cells, it was shown that BIG3 overexpression is one of the important mechanisms causing activation of the estrogen/ERα signaling pathway in the hormone-related growth of breast cancer cells.

Methods

A critical role of transactivation of BIG3 is shown in activation of the estrogen/ER signaling in breast cancer cells.

Results

Knocking-down of BIG3 expression with small-interfering RNA (siRNA) drastically suppressed the growth of breast cancer cells.
Subsequent coimmunoprecipitation 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 ERα, and resulted in suppression of the ERα transcriptional activity.
When BIG3 was present, BIG3 trapped PHB2/REA in the cytoplasm and inhibited its nuclear translocation, and caused enhancement of ERα transcriptional activity.

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