Trichostatin A down-regulates CYP19 transcript and protein levels in MCF-7 breast cancer cells.
Epidemiological and experimental evidence implicates estrogens in the etiology and progression of breast cancer. The biosynthesis of estrogens from androgens is catalyzed by an enzymatic complex designated as aromatase (CYP19). Using quantitative real-time PCR and Western blot analysis, we demonstrated that trichostatin A (TSA) histone deacetylase inhibitor significantly reduced CYP19 transcript and protein contents in MCF-7 breast cancer cells. We also found that TSA lowered CYP19 transcript stability and significantly decreased the transcript's half-life from approximately 6h to 3.5h. Our results from experiments with a protein biosynthesis inhibitor suggest the involvement of an RNase and/or mRNA stabilization protein in CYP19 transcript stabilization. Since malignant tissue aromatase is a significant estrogen producer involved in breast tumor progression, our findings may have clinical implication.
Łuczak
M W
MW
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland.
Jagodziński
P P
PP
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006207:Half-Life; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D012334:RNA, Neoplasm / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C012589:trichostatin A; D001141:Aromatase