Too Sensitive to Estrogen?

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Science  25 Aug 2000:
Vol. 289, Issue 5483, pp. 1259
DOI: 10.1126/science.289.5483.1259a

The growth of normal breast epithelial cells is stimulated dramatically by estrogen. Increased exposure or responsiveness of breast tissue to this hormone is thought to be a risk factor for cancer.

In a search for genetic changes in breast cells that might lead to an altered estrogen response, Fuqua et al. found that a large proportion of breast hyperplasias (microscopic masses of proliferating premalignant cells that can progress to cancer) express a variant form of the estrogen receptor (ERα) that is hypersensitive to estrogen. This variant contains an amino acid change in the region between the hinge and hormone-binding domains, and it shows enhanced binding to the TIF2 co-activator when estrogen levels are low. Expression of this aberrant receptor could convey to breast epithelium an augmented mitogenic signal that would accelerate cancer development. If future clinical studies confirm a link between ERα and breast cancer progression, genetic tests for the variant might help to identify women who would benefit from precautionary measures. — PAK

Cancer Res. 60, 4026 (2000).

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