A mechanism behind resistance to the anti-cancer drug tamoxifen in breast cancer is reported online in Nature. The research could be used to predict the outcome of tamoxifen therapy.
Tamoxifen stops tumour growth by binding to the oestrogen receptor and blocking expression of ERBB2/HER-2 - a receptor that causes cells to divide. Jason Carroll and colleagues identify PAX2 as the regulatory molecule that transmits this blocking signal by switching off the ERBB2 gene. When they looked for PAX2 in tumour samples from patients receiving tamoxifen treatment, they found that high levels of PAX2 are associated with improved survival.
In contrast, drug-resistant tumours have higher levels of another molecule - AIB-1 - which competes with PAX2 in a molecular tug of war to initiate ERBB2/HER-2 expression. Overall, the team find that the ratio of PAX2 to AIB-1 predicts the efficacy of tamoxifen therapy in breast cancer.
Jason Carroll (Cancer Research UK Cambridge Research Institute, UK)
Abstract available online.
(C) Nature press release.
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