Estrogen control of lactate dehydrogenase isoenzyme-5 in human breast cancer.
Determinations of estradiol receptor (ER), progesterone receptor (PR), total lactate dehydrogenase activity (LDH) and electrophoretic separation of LDH isoenzymes were performed in cytosols from 118 samples of primary infiltrating ductal mammary carcinoma. ER + PR+ tumors demonstrated a significant increase in the proportion of the LDH muscle-type isoenzyme (LDH5) as compared to ER-PR- samples (p less than 0.002). Tumors lacking one of the receptors presented intermediate LDH5 percentages. As total LDH activity bore no relation to either the presence or absence of receptors, the increased proportion represents an absolute elevation of LDH5, suggesting that LDH5 may be a promising hormone-dependence marker. As an in vitro model to study whether LDH5 was induced by estradiol via ER, we have used two human breast cancer cell lines, MCF-7 and T47D. In both cell lines LDH5 was the sole isoenzyme. Total ER and PR have been determined by a whole-cell method. In MCF-7 cells (with high ER levels), after incubation with 10(-10) M estradiol, maximal induction of LDH had already been achieved. In relation to T47D (low ER levels) estradiol did not evoke an induction of LDH5 at any concentration examined. In MCF-7 cells, the level of LDH5 induction paralleled processing of ER. The processing effect was rapid, beginning within 5 min of estradiol addition, and was completed within 1 hr. With 10(-6) M tamoxifen, LDH5 induction was suppressed and this effect was reversed by estradiol. Such antiestrogenic effects of tamoxifen on LDH5 have not been observed in T47D cells. Agonistic effects of low doses of tamoxifen on LDH5 were not observed. Our studies suggest that estrogen stimulation of LDH5 involves ER.
Nagai
M A
MA
Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Sonohara
S
S
Brentani
M M
MM
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D005260:Female; D006801:Humans; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008593:Menopause; D008875:Middle Aged; D011959:Receptors, Estradiol / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000378:metabolism
D007527:Isoenzymes; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007770:L-Lactate Dehydrogenase