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Prostate cancer

Studying the classics

Nature Reviews Cancer volume 11, pages 386–387 (2011)Cite this article

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Yuka Nakajima and colleagues examined the function of ERβ in two androgen-insensitive prostate cancer cell lines, DU145 and PC3: DU145 cells express only ERβ but PC3 cells express both ER subtypes. The injection of these cells into nude mice showed that both cell lines grew faster in the presence of oestrogen and that growth was inhibited by an ER antagonist, ICI. Moreover, knockdown of ERβ using RNA interference prevented these effects. Use of a different ER antagonist suggested that the effects of ERβ were not mediated through the classical pathway, in which ERs directly bind oestrogen response elements in gene promotersand activate transcription. The non-classical ER signalling pathway involves the binding of ERs to several different transcription factors, and in a screen for proteins that interact with ERβ the authors pulled out the transcription factor Krüppel-like factor 5 (KLF5), which is a known suppressor of prostate cancer. Overexpression of KLF5 in DU145 cells suppressed the formation of colonies on soft agar and their growth in vivo. Transient transcription assays indicated that ERβ increased KLF5 transcriptional activity, and this was further increased in the presence of ICI but was suppressed by oestrogen.

these results indicate that specific ER antagonists can promote this non-classical pathway, suggesting potential new therapeutic approaches for prostate cancer

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ORIGINAL RESEARCH PAPER

  1. Nakajima, Y. et al. Estrogen regulates tumor growth through a nonclassical pathway that includes the transcription factors ERβ and KLF5. Sci. Signal. 4, ra22 (2011)

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  1. Nicola McCarthy
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McCarthy, N. Studying the classics. Nat Rev Cancer 11, 386–387 (2011). https://doi.org/10.1038/nrc3072

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