Robert A. Orlando

Multiple molecular forms of lactate dehydrogenase and glucose 6‐phosphate dehydrogenase in normal and abnormal human breast tissues

Normal and abnormal breast samples of women were analyzed for multiple molecular forms of lactate dehydrogenase and glucose 6‐phosphate dehydrogenase, using acrylamide disc gel electrophoresis and specific enzyme staining techniques for separation and quantitation. Infiltrating ductal carcinomas demonstrated a significant increase (three‐to six‐fold) in the proportion of LDH‐5 compared to samples of normal breast, fibrocystic disease and fibroadenoma, indicative of a shift toward the muscle‐type lactate dehydrogenase in neoplasia. For glucose 6‐phosphate dehydrogenase, carcinomas were found to contain increased proportions of the fastest migrating species, G6PD‐I. Total enzyme activity/mg DNA was elevated in neoplastic tissues. Little or no alteration in isoenzyme profiles could be related to menopausal status of the patient.

Some Biochemical Characteristics of Human Breast Cancer and Nonmalignant Breast Lesions

Summary Human infiltrating ductal carcinoma of the breast, fibrocystic disease of the breast, and normal human mammary tissues were assayed for their concentration of nucleic acid, lipids, and 11 selected enzymes involved in carbohydrate, lipid, and amino acid metabolism. Comparing infiltrating ductal carcinomas to normal mammary tissue, striking elevations (p <0.001) were seen in pyruvate kinase (100-fold), glucose-6-phosphate, isocitrate and malate dehydrogenases (10-15-fold), free fatty acids and cholesterol (2-3-fold). The RNA/DNA ratios in the carcinomas were unchanged but triglycerides and α-glycerolphosphate dehydrogenase were reduced. Also studied were samples from eight cases of fibrocystic disease, a common nonmalignant proliferative disease of the human breast. Ranking the levels of nucleic acids and lipids and the activities of the enzymes in the tissues studied clearly showed that normal ≦ fibrocystic disease ≦ infiltrating ductal carcinoma. No significant differences in the biochemical characteristics of the carcinomas were found relative to the size of the lesion or to the menopausal state of the patient. These data on infiltrating ductal carcinomas closely resemble the data obtained from single dose 7,12-dimethylbenz [a] anthracene-induced rat mammary carcinomas, suggesting that the latter experimental tumor may represent a valid metabolic model of human breast cancer.

Some Biochemical Characteristics of Rodent and Human Mammary Carcinomas

SummaryIn order to establish valid experimental systems for the study of breast cancer, an examination of the biochemical and morphologic characteristics of transplantable and carcinogen-induced mamma

Pyruvate kinase and total protein are regulated differently during growth of P-815 mastocytoma cells

Total protein content of P-815 mastocytoma cells decreases and then increases in response to initiation of a new growth cycle. As the level increases, the rate of synthesis declines. Both events occur prior to any decrease in the rate of cellular proliferation. These temporal relationships indicate that the rate of protein synthesis reflects the intracellular concentration of protein rather than the cellular growth rate, as has been hypothesized. Pyruvate kinase protein metabolism differs from that of total protein in three ways: (a) accumulation does not stop, (b) the rate of synthesis does not decrease, and (c) only the rate of pyruvate kinase degradation is altered by a factor present in conditioned media. These observations suggest that there are specific mechanisms regulating pyruvate kinase at a post-transcriptional level.