Lactate dehydrogenase (LDH) is an essential enzyme that catalyzes the interconversion of lactate and pyruvate, with consequent effects on aerobic versus anaerobic metabolism. Five isozymes of tetrameric LDH are found in various proportions in most somatic tissues. They are the result of in vivo combination of A and B subunits to form LDH- A4, -A3B1, -A2B2, -A1B3, and -B4. In addition, C subunits are present in male reproductive organs. The different isozymes possess different physical, catalytic, and immunologic properties. The LDH-A4 isozyme is utilized preferentially in anaerobic metabolism. The A, B, and C subunits are each the product of a distinct gene. LDH activity is elevated in human neoplastic disease, particularly in invasive human breast cancers compared to benign proliferative disease and normal breast tissue. In the course of cloning abundantly expressed mRNAs in human cancer cells, we identified a cDNA clone of LDH-B and found that expression of LDH-B mRNA is undetectable in human breast cancer cells that are estrogen receptor positive. In contrast, normal breast epithelial cells and breast cancer cells that are estrogen receptor negative express the LDH-B mRNA. The goal of this project is to determine the mechanism and consequences of the loss of LDH-B4 in steroid receptor-positive breast cancer cells.
