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ErbB‐2 expression in estrogen‐receptor‐positive breast‐tumor cells is regulated by growth‐modulatory reagents
Author(s) -
Taverna Daniela,
Antoniotti Susanna,
Maggiora Piera,
Dati Claudio,
de Bortoli Michele,
Hynes Nancy E.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910560411
Subject(s) - medicine , endocrinology , epidermal growth factor , estrogen , estrogen receptor , messenger rna , biology , cell growth , retinoic acid , receptor , chemistry , cell culture , biochemistry , gene , breast cancer , cancer , genetics
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 (E 2 ), progesterone (Pg), retinoic acid (RA), epidermal growth factor (EGF), insulin (Ins), prolactin (Prl), 12‐ O ‐tetradecanolyl‐phorbol‐13‐acetate (TPA) and dibutyryl‐3′:5′‐cycfic‐AMP (cAMP) on c‐ erb B‐2 promoter activity, RNA and protein expression have been examined. The growth stimulators E 2 and EGF both reduced the level of erbB‐2 protein. However, while E 2 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‐ erb B‐2 promoter activity and RNA amount. TPA and RA also increased promoter activity but neither erb B‐2 mRNA nor protein level was enhanced. The erb B‐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‐ erb B‐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.