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New Estrogen Mechanism Holds Novel Cancer Treatment Promise

Update Date: Sep 29, 2014 04:49 PM EDT

Scientists have discovered a previously unknown estrogen pathway in cells which promotes proliferation and resistance to cancer-drugs which could pave way for novel targetted breast cancer treatments. 

According to a press release, estrogen under stress is known to activate a pathway called the unfolded-protein response or UPR which in turn causes production of molecular proteins that help packing other proteins responsible for cell proliferation.  Scientists have discovered that estrogen can activate the pathway before the cell is stressed.  

"This is a new role for estrogen in the pathology of cancer. Others have shown that stress activates this pathway, helping to protect some tumors. What is new is our finding that estrogen can pre-activate this pathway to protect tumors," said biochemistry Professor David Shapiro of University of Illinois.  

Shapiro explained that binding of estrogen to a receptor floods a cell with calcium which he said is a signal.

"That's a signal to activate the UPR pathway, the stress pathway. It's also a signal that many researchers think has something to do with cell proliferation. The calcium itself may be a proliferation signal. I like to think of this pathway as an assembly line. In order for cells to divide, you're going to have to produce a lot more proteins. The chaperones help you to package, fold up and ship all these proteins," Shapiro said.

Scientists also found that UPR activation can lead to prevention of normal death when the cell is under extreme duress. However when activation under cancer is mild, the cell-death process, also called apoptosis, is prevented. Scientists found that only 15 percent of women who received treatment for estrogen-receptive breast cancer were disease free ten years after diagnosis compared to 80 percent of women in who UPR expression was mild.

"Neal Andruska, who spearheaded the research and carried out the computer analysis of the breast cancer data, found that UPR activation is a very powerful prognostic marker of the course of a woman's disease. Our marker helps identify breast cancers that are likely to be highly aggressive and therefore require intensive therapy," Shapiro said.

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