Steven M. Hill, PhD
Ph.D.: University of Arizona
(Molecular Endocrinology of Breast Cancer)
Breast cancer is the second healing cause of cancer related deaths in American Women. Currently it is estimated that 1 in 9 women will develop breast cancer at some point in her lifetime. Since the normal female breast is responsive to estrogen as well as other hormones, it follows that carcinoma of the breast is for the most part also estrogen and hormone responsive. The molecular aspect of these endocrine responsive tumors and factors regulating endocrine and particularly estrogen responsiveness are the focus on ongoing research in this laboratory. 111
Molecular lesions in the ER of human breast cancer and the development of hormone-resistance. Recent studies by this laboratory and our collaborators have shown that human breast tumors and breast cancer cell lines which are estrogen independent express variant forms of ER mRNA. Using reverse transcriptase polymerase chain reaction (RE-PCR) as well as cloning and sequencing techniques it has been shown that these estrogen receptor (ER) mRNA variants contain deletions of two exons 5 and exon 7) which encode portions of the hormone-binding domain of the ER. These exonic deletions are the result of RNA splicing and thus may be structural and functional, of other ER mRNA variants, and mechanisms which may regulate the expression of the variant ER mRNA over the wild-type ER mRNA. Studies examining the frequency of ER variant expression in clinical breast tumors is also being conducted. Current molecular techniques used in these studies will include, DNA and RNA analysis, RT-PCR analysis, cloning, sequencing, and transfection. The overall goal of this research is to better understand mechanisms involved in the loss of estrogen responsiveness and the development of antiestrogen resistance.
Neuroendocrine influences on mammary cancer. Melatonin is the principal hormone product of the pineal gland and has been shown to be an important regulator of the reproductive physiology of seasonally breeding animals. Numerous studies have also shown that this hormone also plays a role in the development and growth of human neoplasms, particularly endocrine responsive breast tumors, and may be a naturally occurring antiestrogen. Ongoing studies in this laboratory are characterizing the ability of melatonin to suppress the proliferative capacity and to inhibit the expression of ER in ER-positive human breast cancer cells. In addition, the effects of melatonin on estrogen-regulated growth factors is also being examined. These studies will employ a variety of techniques such as Western blot analysis, Northern blot analysis, RNase protection analysis, hormone-binding analysis, and nuclear "Run-On" analysis.
A PubMed listing of research publications for Steven M. Hill, Ph.D.
Structural & Cellular Biology