May 7, 2013

How pregnancy reduces breast cancer risk

Scientists from the FMI have identified a molecular mechanism that may explain how early pregnancy reduces the risk for breast cancer. Their results have been published in the open access journal Breast Cancer Research.

Early pregnancy is the best protective agent against breast cancer. Very young mothers are particularly protected: Their lifelong breast cancer risk is cut in more than half when compared to other women. Even though these facts have been known for decades, scientists did not understand why pregnancy could have such an impact later in life.

Research conducted by Mohamed Bentires Alj’s group at the Friedrich Miescher Institute for Biomedical Research illuminates now some of the molecular and cellular mechanisms responsible for this protective effect.

The scientists could show that early pregnancy changes mammary cell fate. By analyzing gene expression profiles of specific subpopulations of the mammary gland, they found that genes involved in differentiation were up-regulated in mice after pregnancy. In particular, the equilibrium of two signaling cascades, the Wnt and the Notch signaling pathways, was shifted. This pushed the basal stem/progenitor cells in mammary epithelium towards a more differentiated cell fate in mice that gave birth compared to virgin mice. The scientists found that the effect on Wnt signaling was pronounced: Not only were the Wnt4 ligand and genes regulated or stimulated by Wnt down-regulated, but Wnt-inhibiting proteins were also up-regulated. The opposite was true for Notch. What is more, these changes did not disappear after pregnancy, they remained long after the mice gave birth.

“The down-regulation of Wnt is the opposite of what we see in many cancers, and this tightened control of Wnt/Notch after pregnancy may be preventing the runaway growth present in cancer. Our studies pave the way for further investigations to assess whether Wnt inhibitors can mimic the protective effect of early pregnancy” comments Bentires Alj.

Fabienne Meier-Abt, MD-PhD and first author of the paper, commented: “At the time when early pregnancy is the exception rather than the rule in our societies, the identification of ways for mimicking the breast cancer protective effect of early pregnancy is warranted“.

Original publication
Meier-Abt F, Milani E, Roloff T, Brinkhaus H, Duss S, Meyer DS, Klebba I, Balwierz PJ, van Nimwegen E, Bentires-Alj M (2013) Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium. Breast Cancer Res. 2013 Apr 29;15(2):R36

About Mohamed Bentires-Alj
Momo Bentires-Alj’s research is aimed at understanding the basic biochemical and cell biological mechanisms of breast cancer initiation and progression. He and his team focus on the following important areas: normal and neoplastic breast stem cells and roles of protein-tyrosine phosphatases and alterations of the PI3K pathway in metastatic breast cancer. Finally, in a more translational vain, they study the mechanisms of resistance to targeted therapies and monitor the metastatic process and the response to therapy using intravital imaging.
» More about Momo Bentires

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