Date of Graduation
The steroid hormones, estrogen and progesterone, are known to have regulatory functions in normal mammary tissue and in some tumors of the breast. We report here the occurrence, partial purification, and preliminary characterization of peroxidase from bovine mammary tissue, and the presence and steroid hormone influences on peroxidase and lactate dehydrogenase in human breast cancer cells in tissue culture. Six human breast cancer cell lines and one human breast cell line derived from normal epithelial cells have been assayed for the presence and estrogen-inducibility of peroxidase and lactate dehydrogenase. Peroxidase was absent in four of seven human breast cell lines surveyed. It was found in two of five assays in one human breast cancer cell line (T47D) and in one of three assays in another (BT-20). The peroxidase activity was extremely unstable as compared to that from bovine mammary tissue. These data suggest that peroxidase is likely a poor marker for estrogen responsiveness in breast cancer. Lactate dehydrogenase was found in all cell lines tested and consistently estrogen-stimulated in one (MCF-7) and occasionally (possibly serum lot dependent) in another (T47D). Additionally, we report that progestins alone at physiological concentrations stimulate lactate dehydrogenase in T47D human breast cancer cells. This stimulation was shown to be dose-responsive. The effect is optimal after three days of treatment, after which time a decline in response is observed. The only isozyme detectable is LDH-5, the muscle type isozyme. It is this isozyme which is stimulated in response to progestin treatment. The effect is specific for progestins with no stimulation of the enzyme seen following treatment with physiological levels of an estrogen, an androgen, or a glucocorticoid. Treatment with transcriptional and translational inhibitors in the presence of progestins suggest that the effect is dependent on new protein and RNA synthesis.
Hagley, Rodney Dale, "Lactate Dehydrogenase And Peroxidase In Mammary Cells, Normal And Cancerous, With Special Reference To Progestin Effects On Lactate Dehydrogenase In The Human Breast Cancer Cell Line T47D." (1986). Graduate Theses, Dissertations, and Problem Reports. 8973.