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Development of resistance to therapy continues to be a serious clinical problem in breast cancer management. Cancer stem/progenitor cells have been shown to play roles in resistance to chemo- and radiotherapy. Here, we examined their role in the development of resistance to the oestrogen receptor antagonist tamoxifen. Tamoxifen-resistant cells were enriched for stem/progenitors and expressed high levels of the stem cell marker Sox2. Silencing of the SOX2 gene reduced the size of the stem/progenitor cell population and restored sensitivity to tamoxifen. Conversely, ectopic expression of Sox2 reduced tamoxifen sensitivity in vitro and in vivo. Gene expression profiling revealed activation of the Wnt signalling pathway in Sox2-expressing cells, and inhibition of Wnt signalling sensitized resistant cells to tamoxifen. Examination of patient tumours indicated that Sox2 levels are higher in patients after endocrine therapy failure, and also in the primary tumours of these patients, compared to those of responders. Together, these results suggest that development of tamoxifen resistance is driven by Sox2-dependent activation of Wnt signalling in cancer stem/progenitor cells.

Nineteen substituted 2-phenylbenz-X-azoles, which are intermediates for the synthesis of dyes, were prepared from p-aminosalicylic acid (PAS). Substituents in the phenyl ring are 2′-hydroxy and/or 4′-amino and 4′-alkylamido with alkyl chains ranging from C1 to C15. The preferred route of the synthesis is discussed. The melting points and the Rf values are correlated with the structure. An extensive discussion of the electronic absorption spectra, involving other compounds with the same general structure, is reported.