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Breast cancer drug fulvestrant appears more effective in the presence of CK8 and CK18
Date:3/10/2010

BLOOMINGTON, Ind. -- Women's responsiveness to the second-line breast cancer drug fulvestrant may depend on whether the cancer cells are expressing two key proteins, Indiana University Bloomington scientists report in this month's Cancer Biology & Therapy.

Fulvestrant appeared to exert maximum anti-cancer effects in vitro when cells produced normal or elevated quantities of the cytokeratins CK8 and CK18, structural proteins that help give the nucleus its shape.

For fulvestrant to work well, the cells must also be responsive to estrogen, and producing the estrogen receptor ER-alpha. ER-alpha's importance to fulvestrant's anti-estrogenic action had been established in previous reports. The present study confirms fulvestrant's binding relationship to ER-alpha, while also showing two other proteins, cytokeratins 8 and 18, can strongly enhance fulvestrant's anti-estrogenic activity. Testing for the presence of these three proteins, and perhaps many others, could help doctors decide whether fulvestrant should be prescribed to their patients.

"We need an effective panel of markers that inform physicians about what treatment options will be most beneficial to patients," said Medical Sciences Program Bloomington cancer biologist Kenneth Nephew, who led the study. "These three gene products should be investigated further to determine whether they should be included in that panel."

Medical Sciences Program Bloomington is a division of the IU School of Medicine. Nephew is a professor of cellular and integrative physiology, and obstetrics and gynecology.

"Normal" breast cancer cells can grow faster in the presence of estrogen, a hormone. Estrogen attaches to receptors embedded in the cancer cell, such as ER-alpha in the cytoplasm and nucleus. The estrogen-ER complex can then act to turn on genes or amplify their expression. Not all cancer cells are responsive to estrogen, however, or to fulvestrant, which counteract
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Contact: David Bricker
brickerd@indiana.edu
812-856-9035
Indiana University
Source:Eurekalert  

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