Regulation of gene activation by the estrogen receptor (ER) is complex and involves co-regulatory
proteins, oncoproteins (such as Fos and Jun), and phosphorylation signaling pathways. Rubino D et al 1999 reported
the cloning and initial characterization of a novel protein, Brx, that contains a region of identity to the
oncogenic Rho-guanine nucleotide exchange (Rho-GEF) protein Lbc, and a unique region capable of
binding to nuclear hormone receptors, including the ER. Western and immunohistochemistry studies
showed Brx to be expressed in estrogen-responsive reproductive tissues, including breast ductal
epithelium. Brx bound specifically to the ER via an interaction that required distinct regions of ER and
Brx. Furthermore, overexpression of Brx in transfection experiments using an estrogen-responsive
reporter revealed that Brx augmented gene activation by the ER in an element-specific and
ligand-dependent manner. Taken
together, these data suggest that Brx represents a novel modular protein that may integrate cytoplasmic
signaling pathways involving Rho family GTPases and nuclear hormone receptors.
Miller BT, et al 2000 reported the expression of brx proto-oncogene in normal ovary and in
epithelial ovarian neoplasms
They identified a protein, Err, that interacted with
estrogen receptor. Sequence analysis determined that Err is a novel member
of the Dbl family of oncoproteins involved in signaling pathways that regulate
cell growth.
A polyclonal antiserum directed against the Err protein was used
to perform immunolocalization on sections from 5 normal ovaries and 20 ovarian
neoplasms. Err protein was localized to the cytoplasm of granulosa cells from
mature graafian follicles, the corpus luteum, and islands of hilar cells in
normal ovaries. In tumors with low malignant potential and ovarian carcinomas
the neoplastic epithelium stained strongly for Err protein