Newly appreciated membrane estrogen receptor important therapeutic target for bre...( PROVIDENCE RI New research at Rhode...),Health

PROVIDENCE, RI New research at Rhode Island Hospital has uncovered the biological effects of a novel membrane estrogen receptor, a finding that has potential implications for hormonal therapy for breast cancer. The study is published in the July edition of the journal Molecular Endocrinology. This new study by Edward Filardo, MD, and his research team further supports earlier published work by the group that linked the transmembrane receptor, GPR30/GPER-1, to specific estrogen binding, rapid estrogen signaling and breast cancer metastasis. "What is exciting about this new work," says Filardo, "is that it provides some insight into the influence of GPR30 at the cellular level. It shows that estrogen action through GPR30 allows for breast tumor cell survival, and not breast tumor cell proliferation." Prior studies by Filardo's group showed that estrogen acts through GPR30 to promote the rapid release of preformed growth factors that are tethered to the surface of breast cancer cells. Their latest study was conducted in an effort to better understand the mechanism by which GPR30 triggered the release of epidermal growth factor (EGF) polypeptides from the surface of breast cancer cells.

The investigator's found that the "growth factors" did not promote cellular growth, which by itself is not a novel finding. It has long been appreciated that EGF-related factors are also important in other cellular activities such as cellular survival. Filardo and the research team, however, found that estrogen action through GPR30 had a more profound effect on tumor cell survival. They found that GPR30 promoted the assembly of what is called a "provisional extracellular matrix" -- a crucial event in cellular survival. More specifically, they found that release of growth factor by GPR30 required the activation of a latent adhesion receptor (known as integrin 51).

Filardo says, "Activation of integrin 51 by GPR30 is a signif
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