erbB-2 expression in estrogen-receptor-positive breast-tumor cells is regulated by growth-modulatory reagents.
It has previously been shown that, in the estrogen-receptor-positive breast-tumor cell lines T47D and ZR75.1, the erbB-2 protein and mRNA content are controlled negatively and positively by, respectively, estrogens and anti-estrogens. Since estrogens have a positive effect on cell proliferation, while anti-estrogens inhibit cell growth, the results suggested that there may be an inverse correlation between growth and erbB-2 expression. We have now examined this matter further. The effect of various growth-modulatory agents including estrogen (E2), progesterone (Pg), retinoic acid (RA), epidermal growth factor (EGF), insulin (Ins), prolactin (Prl), 12-O-tetradecanolyl-phorbol-13-acetate (TPA) and dibutyryl-3':5'-cyclic-AMP (cAMP) on c-erbB-2 promoter activity, RNA and protein expression have been examined. The growth stimulators E2 and EGF both reduced the level of erbB-2 protein. However, while E2 clearly repressed erbB-2 transcription, in the case of EGF, neither mRNA nor transcription were decreased. Of the agents which inhibit the growth of T47D and ZR75.1 cells--Pg, Prl, cAMP, RA and TPA--only Pg and cAMP caused an increase in the erbB-2 protein level. Pg and cAMP positively influenced c-erbB-2 promoter activity and RNA amount. TPA and RA also increased promoter activity but neither erbB-2 mRNA nor protein level was enhanced. The erbB-2 protein expression in cultures of T47D and ZR75.1 cells at different densities was also analyzed. Both the level of erbB-2 protein and c-erbB-2 promoter activity rose markedly in confluent cultures, suggesting a transcriptional mechanism of control. In conclusion, the data suggest that the effects of various agents on erbB-2 expression are complex and cannot be explained simply as reflecting the growth state of the cells.
Taverna
D
D
Friedrich Miescher Institute, Basel, Switzerland.
Antoniotti
S
S
Maggiora
P
P
Dati
C
C
De Bortoli
M
M
Hynes
N E
NE
D001483:Base Sequence; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002452:Cell Count; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008969:Molecular Sequence Data; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003994:Bucladesine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D004958:Estradiol; D006133:Growth Substances; D007328:Insulin; D011374:Progesterone; D011388:Prolactin; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013755:Tetradecanoylphorbol Acetate; D014212:Tretinoin