Studies on Certain Cytoplasmic Enzymes and Specific Estrogen Receptors in Human Breast Cancer and in Nonmalignant Diseases of the Breast

Summary

Samples of normal breast tissue, fibrocystic disease, fibroadenomas, and infiltrating ductal carcinomas were examined for several cytoplasmic enzymes and specific estrogen-binding capacity, as well as for the levels of RNA, DNA, and protein. Compared with normal breast tissue, the activities per mg DNA of pyruvate kinase, glucose 6-phosphate dehydrogenase, isocitrate dehydrogenase, hexokinase, glucose phosphate isomerase, and aspartate aminotransferase were significantly elevated in carcinomas. Furthermore, the activities of these enzymes were also significantly higher in the carcinomas, compared with those of samples of fibrocystic disease and fibroadenoma. Overall, there appeared to be little difference in the biochemical parameters measured in this comparison of normal breast tissue, fibrocystic disease, and fibroadenoma when the data were normalized by expression of results per mg DNA. A notable exception was the decrease in activity in α-glycerol phosphate dehydrogenase, which was highest in normal breast tissue and significantly decreased in all the breast diseases examined. Neither the age of the patient at the time the tumor was removed nor the presence of metastatic lesions was apparently related to the biochemical characteristics, although the carcinomas from women 70 years or older showed somewhat higher activities of glucose phosphate isomerase, lactate dehydrogenase, and glucose 6-phosphate dehydrogenase.

Carcinomas that possessed specific estrogen-binding capacity (>7 fmoles/mg protein), as estimated by sucrose gradient centrifugation of tumor cytosols, had lower activities of glucose 6-phosphate dehydrogenase, isocitrate dehydrogenase, and pyruvate kinase and slightly higher levels of DNA. The data reported here indicate that infiltrating ductal carcinoma of the breast presents with certain metabolic alterations that are not shared by nonmalignant breast diseases. Carcinomas that are potentially hormone responsive demonstrate a different enzyme activity profile from that of tumors that are potentially hormone independent.