A possible regulatory role of 17beta-estradiol and tamoxifen on glyoxalase I and glyoxalase II genes expression in MCF7 and BT20 human breast cancer cells.
The glutathione-dependent glyoxalases system, composed of glyoxalase I (GloI) and glyoxalase II (GloII) enzymes, is involved in the detoxification of methylglyoxal, a by-product of cell metabolism. Aberrations in the expression of glyoxalase genes in several human cancers have been reported. Sometimes, these aberrations seem to differ depending on the organs and on the sensitivity of the tumours to estrogens, as we previously detected in the hormone-responsive breast cancer compared to the hormone-independent bladder cancer. To investigate a possible regulatory role of estrogens, as well as antiestrogens, on glyoxalases system, estrogen receptor (ER)-positive MCF7 and ER-negative BT20 human breast cancer cells were cultured in the presence of 17beta-estradiol (E2) and tamoxifen (TAM) performing two independent experiments. After a 24 h or 4 days treatment, we evaluated GloI and GloII mRNA levels, by Ribonuclease Protection Assay (RPA), enzymatic activities spectrophotometrically and cell proliferation by [3H]thymidine incorporation. We found that both steroid molecules affected glyoxalases gene expression and proliferation in a different manner in the cell lines. The modifications in mRNA levels were accompanied by parallel changes in the enzymatic activities. The possibility that modulation of glyoxalase genes by E2 and TAM are due to the presence of estrogen response elements (ERE) or cross-talk mechanisms by proteins of the estrogen signal transduction pathways are discussed. Knowledge regarding the regulation of glyoxalases by E2 and TAM may provide insights into the importance of this enzymes in human breast carcinomas in vivo.
Rulli
Antonio
A
Department of Surgical Sciences, University of Perugia, Perugia, Italy.
Antognelli
Cinzia
C
Prezzi
Eleonora
E
Baldracchini
Francesca
F
Piva
Francesco
F
Giovannini
Elvio
E
Talesa
Vincenzo
V
D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology*; D013869:Thiolester Hydrolases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
D004958:Estradiol; D004965:Estrogen Antagonists; D007791:Lactoylglutathione Lyase; D012333:RNA, Messenger; D013629:Tamoxifen; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase