Interaction between estradiol and cAMP in the regulation of specific gene expression.
The mRNA levels of LIV-1 and pS2, two estrogen-responsive genes, are increased by the agents, cholera toxin (CT) plus 3-isobutyl-l-methylxanthine (IBMX), which cause an increase in cAMP in MCF-7 human breast cancer cells. The simultaneous addition of estradiol and CT/IBMX results in a synergistic induction of the two mRNAs. The changes in mRNA reflect changes in transcription of the two genes. Interestingly, the addition of CT/IBMX to estradiol not only causes a greater increase in transcription rate but the increase is longer-lasting that seen with the hormone alone. Stimulation of mRNA levels by CT/IBMX, but not by estradiol, was prevented by cycloheximide. Stimulation by both estradiol and by CT/IBMX was prevented by the antiestrogen, ICI 164387. Transcription of LIV-1 and pS2 genes is by both estradiol and cAMP, via separate mechanisms both requiring the estrogen receptor.
el-Tanani
M K
MK
Department of Biochemistry, University of Liverpool, UK.
Green
C D
CD
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001943:Breast Neoplasms; D002277:Carcinoma; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011959:Receptors, Estradiol / Q000502:physiology; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D004965:Estrogen Antagonists; D009363:Neoplasm Proteins; D010726:Phosphodiesterase Inhibitors; D053284:Polyunsaturated Alkamides; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011959:Receptors, Estradiol; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D004958:Estradiol; C051781:ICI 164384; D002772:Cholera Toxin; D003513:Cycloheximide; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine