J. Mark Cline, D.V.M., Ph.D.
Work in my laboratory focuses on histopathologic and immunohistochemical methods for characterization of pre-neoplastic lesions and neoplasms. My work concerns the effect of hormonal therapies (hormone replacement after menopause, oral contraceptives, and others) on breast and uterine cancer risk. This work involves the characterization of regulatory changes and pre-cancerous lesions in the endometrium and mammary gland of macaques receiving the various hormonal therapies. Endpoints in these studies are changes in expression of proliferation markers (for example, Ki-67), estrogen and progesterone receptors, growth factor receptors, markers of cell death (apoptosis), and the development of morphologically detectable preneoplastic changes. Soy isoflavones (phytoestrogens) are also being studied, as a dietary alternative to postmenopausal hormonal replacement therapy. Work to date indicates that hormonal regulation of the breast and endometrium differ in postmenopausal animals, and that the combined estrogen-progestin therapy that prevents endometrial cancer increases proliferation in breast epithelial cells and may therefore increase the risk of breast cancer. Our most recent and exciting results indicate that dietary soy supplementation may decrease estrogen-induced cell proliferation and cancer risk in the breast and uterus.
FIGURE 1: Breast epithelium stained with an antibody to the proliferation marker Ki67. Brown staining indicates proliferation and an associated increase in cancer risk.
FIGURE 2: Ki67 (proliferation marker) staining of breast and endometrium, in animals given estrogen (E2) or a high-soy diet (Soy) or the combination. These results suggest that dietary soy may decrease breast and uterine cancer risk.