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 intracellular association 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 by Northern blot and RNase protection analysis in human breast cancer cells that are steroid receptor positive. In contrast, normal breast epithelial cells and breast cancer cells that are steroid receptor negative express the LDH-B mRNA. LDH-A and LDH-C cDNA clones were isolated by RT-PCR. Northern blot analysis using the LDH-A and -C probes demonstrated that all tested breast cancer-derived cell lines expressed LDH-A RNA but there was no expression of LDH-C RNA. An immunoblot assay for LDH-B was developed. Immunoblots confirmed that steroid receptor positive human breast cancer cell lines do not express detectable levels of LDH-B protein. Semi-quantitative RT-PCR assays are under development to measure LDH, estrogen receptor and progesterone receptor mRNAs in biological tissues.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Special Emphasis Panel (LP)
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National Cancer Institute Division of Clinical Sciences
United States
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