三苯氧胺常用于乳腺癌治療，但一部分患者會變得對治療方法產(chǎn)生抵抗力,，她們的癌癥更可能復發(fā),。對乳腺癌中雌激素受體與ERBB2/HER-2通道之間的關系所做的一項研究,，為了解三苯氧胺的作用機制及三苯氧胺抗藥性的基礎提供了線索。這項新的研究工作表明,，乳腺癌中ErbB2的主動抑制需要Pax2,，Pax2的減少引起由ErbB2驅(qū)動的抗三苯氧胺細胞的生長。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 456, 663-666 (4 December 2008) | doi:10.1038/nature07483
Regulation of ERBB2 by oestrogen receptor–PAX2 determines response to tamoxifen
Antoni Hurtado1, Kelly A. Holmes1, Timothy R. Geistlinger2, Iain R. Hutcheson3, Robert I. Nicholson3, Myles Brown2, Jie Jiang4, William J. Howat1, Simak Ali4 & Jason S. Carroll1
1 Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
2 Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
3 Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, UK
4 Imperial College London, Hammersmith Hospital, London W12 0NN, UK
Crosstalk between the oestrogen receptor (ER) and ERBB2/HER-2 pathways has long been implicated in breast cancer aetiology and drug response1, yet no direct connection at a transcriptional level has been shown. Here we show that oestrogen–ER and tamoxifen–ER complexes directly repress ERBB2 transcription by means of a cis-regulatory element within the ERBB2 gene in human cell lines. We implicate the paired box 2 gene product (PAX2), in a previously unrecognized role, as a crucial mediator of ER repression of ERBB2 by the anti-cancer drug tamoxifen. We show that PAX2 and the ER co-activator AIB-1/SRC-3 compete for binding and regulation of ERBB2 transcription, the outcome of which determines tamoxifen response in breast cancer cells. The repression of ERBB2 by ER-PAX2 links these two breast cancer subtypes and suggests that aggressive ERBB2-positive tumours can originate from ER-positive luminal tumours by circumventing this repressive mechanism. These data provide mechanistic insight into the molecular basis of endocrine resistance in breast cancer.
