Research ArticleBreast Cancer

Progesterone/RANKL Is a Major Regulatory Axis in the Human Breast

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Science Translational Medicine  24 Apr 2013:
Vol. 5, Issue 182, pp. 182ra55
DOI: 10.1126/scitranslmed.3005654

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3D Without the Glasses

Biomedical research has the lofty goal of adding to our understanding of biology in the hope that we can improve human health. However, there are difficulties—both ethical and logistic—of performing experiments in humans. One way researchers have overcome these hurdles is through the use of cell culture or animal models. Yet, these models sometimes don’t accurately represent human biology, especially in complex tissues. Now, Tanos et al. develop an ex vivo three-dimensional model using fresh breast tissue microstructures to examine the role of the progesterone-mediator RANKL in human breast.

They found that although progesterone failed to induce RANKL in cell lines and dissociated breast tissue, in their microstructures, RANKL expression responded to progesterone and was required for progesterone-induced breast tissue proliferation. They validated these findings in samples from human breast epithelium. These studies could have clinical relevance: The RANKL inhibitor denosumab is currently used in the clinic to treat bone disease and could be repurposed to block breast epithelial proliferation in breast cancer.

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