Alteration of glyoxalase genes expression in response to testosterone in LNCaP and PC3 human prostate cancer cells.
Glyoxalase system, a ubiquitous detoxification pathway protecting against cellular damage caused by potent cytotoxic metabolites, is involved in the regulation of cellular growth. Aberrations in the expression of glyoxalase genes in several human cancers have been reported. Recently, we described a possible regulatory effect by estrogens on glyoxalase genes in human breast cancer cell lines. This result, along with those ones regarding changes in glyoxalases activity and expression in other human hormone-regulated cancers, such as prostate cancer, has prompted us to investigate whether also androgens, whose functional role in prostate cancer pathogenesis is well known, could modulate glyoxalases gene expression. Therefore, we treated LNCaP androgen-responsive and PC3 androgen-independent human prostate cancer cell lines with testosterone at the concentrations of 1 nM and 100 nM. After a two days treatment, glyoxalases mRNA levels as well as cell proliferation were evaluated by real-time RT-PCR analysis and [3H]thymidine incorporation, respectively. Results pointed out that testosterone affects the expression of glyoxalase system genes and cell proliferation in a different manner in the two cell lines. The possibility that modulation of glyoxalase genes expression by testosterone is due to glyoxalases-mediated intracellular response mechanisms to the androgen-induced oxidative stress or to the presence of androgen response elements (ARE) in glyoxalase promoters are discussed. Knowledge regarding the regulation of glyoxalases by testosterone may provide insights into the importance of these enzymes in human prostate carcinomas in vivo.
Antognelli
Cinzia
C
Department of Experimental Medicine, University of Perugia, Perugia, Italy.
Del Buono
Chiara
C
Baldracchini
Francesca
F
Talesa
Vincenzo
V
Cottini
Emanuele
E
Brancadoro
Celestino
C
Zucchi
Alessandro
A
Mearini
Ettore
E
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000728:Androgens; D047072:Aromatase Inhibitors / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000096:biosynthesis / Q000235:genetics*; D000077289:Letrozole; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology; D011765:Pyruvaldehyde / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020218:Response Elements / Q000235:genetics; D013739:Testosterone / Q000494:pharmacology*; D013869:Thiolester Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D014230:Triazoles / Q000494:pharmacology; D000099301:Hydroxyacylglutathione Hydrolase
D000728:Androgens; D047072:Aromatase Inhibitors; D004958:Estradiol; D007791:Lactoylglutathione Lyase; D000077289:Letrozole; D009363:Neoplasm Proteins; D009570:Nitriles; D011765:Pyruvaldehyde; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013739:Testosterone; D013869:Thiolester Hydrolases; D014230:Triazoles; D000099301:Hydroxyacylglutathione Hydrolase