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Scientists Discover New Role for Estrogen in the Pathology of Breast Cancer

Scientists have discovered a previously unknown mechanism by which estrogen prepares cells to divide, grow and, in the case of estrogen-positive breast cancers, resist cancer drugs. The researchers say the work reveals new targets for breast cancer therapy and will help doctors predict which patients need the most aggressive treatment.

The University of Illinois team reports its findings in the journal Oncogene.

Estrogen pre-activates the unfolded-protein response (UPR), a pathway that normally protects cells from stress, the researchers report. The UPR spurs the production of molecular chaperones that prepare cells to divide and grow. Without chaperone proteins to do the work of folding and packaging other proteins, cells including cancer cells cannot divide. For this reason, chaperones are a popular target for new cancer therapies.

Activation of the UPR is known as a normal response to stress when a cell lacks adequate oxygen or nutrients, for example, or is exposed to cancer-killing drugs. UPR activation prepares the cell for major changes associated with cell growth, division and survival under stress.

It wasn't known before this study, however, that estrogen initiates this pathway before such stresses appear, said University of Illinois biochemistry professor David Shapiro, who led the new analysis with lead author, M.D.-Ph.D.-student Neal Andruska.

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