(Philadelphia, PA) - In the pursuit of novel cancer therapies, researchers at the University of Pennsylvania School of Medicine describe new mechanisms by which the hormone prolactin induces the growth and spread of breast cancer, a disease that affects one in nine women.

As a hormone, prolactin is necessary for the production of breast milk. However, its role in stimulating the growth of breast cancer has been only recently recognized in humans, as recent studies have found that prolactin is made by human breast cancer and that elevations in prolactin levels in the blood significantly increase the risk of developing this disease.

In the report, appearing this month in the Proceedings of the National Academy of Sciences, researchers describe that the alteration of the structure of one protein that binds prolactin results in a dramatic inhibition of the growth of breast cancer in the lab. This finding challenges the current dogma of how protein hormones like prolactin function and also provides researchers with new strategies in their therapeutic attack on breast cancer.

"Traditionally, it was thought that protein hormones, like prolactin, only work on the outside of cells - as if their only job was just to hit the 'on' switch," said Charles V. Clevenger, MD, PhD, associate professor in the Penn Department of Pathology and Laboratory Medicine.

"Contrary to established theory, our research has shown that prolactin combines with another protein called cyclophilin B to physically enter the cell and directly activate the process that turns on genes and trigger the growth of breast cancer cells."

"Here we show that prolactin clearly works inside the cell to turn on genes", said Michael Rycyzyn, a postdoctoral fellow in the Clevenger lab and co-author of this study, "and by using modified forms of cyclophilin B we can stop this process and block the growth of breast cancer." In doing this, their lab has uncovered a new pathway through which hormones work, and in turn, discovered a target-rich environment for cancer researchers to explore.

The research presented in this study was provided by grants from the National Institutes of Health and the American Cancer Society.

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Editor's Note:
You can find the original article online at www.pnas.org





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