Steven Hill, PhD, School of Medicine>
The primary focus of Dr. Hill’s research is the molecular mechanisms of signal transduction cross- talk in breast cancer. Breast cancer is an endocrine-responsive neoplasm and as such is responsive to a variety of endocrine and growth factor stimuli. A complete understanding of the factors regulating the proliferation breast cancer, as well as an understanding of how these various hormones and factors cross-talk with each other to regulate breast cancer cell growth, is crucial to development of more potent breast cancer therapies. Dr. Hill’s laboratory has conducted extensive studies examining the role of mutated estrogen receptors in the development of an estrogen-insensitive/tamoxifen-resistant phenotype in breast cancer. They have identified variant forms of the estrogen receptor that can function independent of hormone stimulation and can act to constitutively drive the mitogenic estrogen-response pathway in breast cancer. More recently, Dr. Hill’s laboratory has demonstrated that the pineal hormone melatonin has significant inhibitory effects on the development and growth of human breast cancer. Furthermore, their studies have elucidated that melatonin can potentiate the actions of retinoic acid, a vitamin A derivative, to induce cell death in human breast tumor cells in culture, to prevent the development of carcinogen-induced breast cancer in rats and to induce the regression of over 70% of established breast tumors in rats. These studies currently are being moved into human clinical trials. Finally, Dr. Hill, in collaboration with investigators at Tulane Cancer Center and Xavier University, is examining the cross-talk of signaling pathways such as the melatonin receptor with the retinoic acid receptor and estrogen-receptor in both breast and prostate cancer and how these pathways can be manipulated to provide enhanced therapeutic advantage.