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Estrogen control of lactate dehydrogenase isoenzyme‐5 in human breast cancer
Author(s) -
Nagai M. A.,
Sonohara S.,
Brintani M. M.
Publication year - 1988
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910410104
Subject(s) - lactate dehydrogenase , estrogen receptor , tamoxifen , endocrinology , medicine , isozyme , estrogen , antiestrogen , receptor , progesterone receptor , biology , cancer cell , mammary gland , chemistry , cancer , breast cancer , enzyme , biochemistry
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 (LDH 5 ) as compared to ER‐PR‐ samples ( p < 0.002). Tumors lacking one of the receptors presented intermediate LDH 5 percentages. As total LDH activity bore no relation to either the presence or absence of receptors, the increased proportion represents an absolute elevation of LDH 5 , suggesting that LDH 5 may be a promising hormone‐dependence marker. As an in vitro model to study whether LDH 5 was induced by estradiol via ER, we have used two human breast cancer cell lines, MCF‐7 and T47D. In both cell lines LDH 5 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 LDH 5 at any concentration examined. In MCF‐7 cells, the level of LDH 5 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, LDH 5 induction was suppressed and this effect was reversed by estradiol. Such antiestrogenic effects of tamoxifen on LDH 5 have not been observed in T47D cells. Agonistic effects of low doses of tamoxifen on LDH 5 were not observed. Our studies suggest that estrogen stimulation of LDH 5 , involves ER.