2009 Faculty Researchers

Dennis B. Lubahn, PhD

Finding new functions for hormones, receptor proteins and genes: a molecular genetics approach to exploring the roles of estrogens, phytoestrogens, and estrogen receptors in human disease, particularly prostate cancer

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Department

Biochemistry and Child Health

Office Location

110A ASRC

Phone #:

Office: (573) 884-6781
Fax: (573) 882-7748

Summary

Do phytoestrogens in herbal medicines (dietary supplements in America) really help in the treatment of cancer?

One of the long term goals of my research program is to find novel functions for both estrogens and estrogen response proteins, and then to identify the molecular mechanisms mediating these functions. This research will lead to a better understanding of estrogens' developmental, physiological, and biochemical roles in humans, and additionally will add to our general understanding of how endogenous estrogens and estrogenic chemicals in the environment can impinge upon human health. To pursue these research goals, we "knocked out" the estrogen receptor (ER) gene in mice via homologous recombination and asked the following question: Would an ER-minus mouse, which lacked the classic fu1llength ER protein, respond to any known estrogen, estrogen metabolite, or exogenous (natural, like phytoestrogens, or synthetic) estrogen analog? IfER-minus mice did respond, then we would know that at least one estrogen response protein other than ER exists. The working hypothesis was that several non-ER response proteins exist and that in transgenic ER-minus mice we would see a response to some estrogens. We decided to test the phytoestrogen, genistein, and other additional phytoestrogens, either as pure compounds or as part of complex herbal extracts for their ability to affect prostate cancer progression in the TRAMP prostate cancer mouse model in ERaKO and wild type genetic backgrounds. We have found that genistein requires ERa to exert its protective effects suggesting that the estrogen receptor is important in prostate cancer treatments by other phytoestrogens as well. ERbKO TRAMP and double ERalERBKO mice will also be tested with several other potential anti-carcinogenic compounds found in herbal medicines to see ifthere are additional non-ERa molecular pathways for phytoestrogen action in cancer therapy. Other phytoestrogens and their plant source to be tested in these