title: Effect of sodium butyrate on estrogen receptor and epidermal growth factor receptor gene expression in human breast cancer cell lines.
abstract: Estrogen receptor (ER) binding has been shown to decrease in breast cancer cell lines exposed to sodium butyrate; however, the underlying mechanisms are unknown. In MCF-7 breast cancer cells, butyrate caused a rapid time- and concentration-dependent decrease in ER mRNA levels, apparent by 3 h at 3 mM butyrate. ER gene transcription rate was decreased and cycloheximide co-treatment did not relieve this inhibitory effect, suggesting that the butyrate effect was not dependent on ongoing protein synthesis. In both MCF-7 and T-47D cells the decrease in ER mRNA was mirrored by an increase in the level of epidermal growth factor receptor (EGF-R) mRNA. A marked inverse relationship exists between ER and EGF-R in human breast cancer biopsies and cell lines, and the reciprocal modulation of these genes by butyrate suggests that the expression of ER and EGF-R may be co-regulated. This relationship was further investigated in lines expressing only one or the other receptor. In the ER-positive EGF-R-negative line, MDA-MB-134-VI, butyrate exposure decreased ER mRNA levels, implying that the regulation of ER mRNA by butyrate is independent of EGF-R expression. However, butyrate decreased EGF-R mRNA in two ER-negative lines, MDA-MB-231 and HBL-100. As this effect differed from that in ER-positive lines, the regulation of EGF-R may depend on the expression of ER. The possibility that ER and EGF-R gene expression are closely linked has implications in the understanding of progression of human breast cancers to a hormone-independent phenotype and for the use of ER and EGF-R levels as independent prognostic indicators.
authors.affiliation: Cancer Biology Division, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: A
authors.initials: A
authors.lastname: deFazio
authors.forename: Y E
authors.initials: YE
authors.lastname: Chiew
authors.forename: C
authors.initials: C
authors.lastname: Donoghue
authors.forename: C S
authors.initials: CS
authors.lastname: Lee
authors.forename: R L
authors.initials: RL
authors.lastname: Sutherland
mesh_terms: D001943:Breast Neoplasms; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D015342:DNA Probes; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D002087:Butyrates; D015342:DNA Probes; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D020148:Butyric Acid; D003513:Cycloheximide; D066246:ErbB Receptors