Modulation of estrogen receptor and epidermal growth factor receptor mRNAs by phorbol ester in MCF 7 breast cancer cells.
Previous studies have demonstrated an inverse relationship between estrogen receptor (ER) and epidermal growth factor receptor (EGF-R) gene expression in human breast cancer cells. This relationship was further investigated in MCF 7 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). Exposure to 10 nM TPA resulted in a time-dependent increase in EGF-R mRNA, first apparent at 3 h and maximal between 9 and 24 h. There was a concomitant fall in ER mRNA with a maximum decline to 15-20% of control between 12 and 24 h. Although EGF-R mRNA levels declined between 24 and 72 h, both EGF-R mRNA and EGF-R binding remained above control levels and this was accompanied by a sustained depression of ER mRNA. These data support the view that ER and EGR-R gene expression is inversely regulated in human breast cancer and describe for the first time an inhibitory effect of a phorbol ester on steroid hormone receptor gene expression.
Lee
C S
CS
Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, N.S.W., Australia.
Koga
M
M
Sutherland
R L
RL
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D066246:ErbB Receptors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate