Estrogens and glucocorticoids induce the expression of c-erbB2/NEU receptor in Ishikawa human endometrial cells.
We investigated the effects of estrogens and other steroid hormones on c-erbB2 gene expression in Ishikawa human endometrial adenocarcinoma cells. We have found that the c-erbB2/NEU transcripts are present in the Ishikawa endometrial cell line as well as in human endometrial adenocarcinoma cells. Both cell types express the 4.6 and 2.3 kb c-erbB2 mRNAs. Estradiol significantly increased in a time- and dose-dependent manner the content of c-erbB2 mRNA and the concentration of NEU protein in Ishikawa cell extracts, while progesterone was devoid of any activity. The effect of estradiol was partially reversed by the antiestrogen 4-hydroxytamoxifen, which, however, given alone exhibited agonist effects. Glucocorticoid dexamethasone augmented in a time- and dose-dependent fashion the content of c-erbB2 mRNA and the concentration of NEU protein in Ishikawa cell extracts. The antiglucocorticoid RU 486 acted as a glucocorticoid agonist increasing c-erbB2 gene activation. To our knowledge, this is the first report documenting the induction by steroid hormones of c-erbB2 gene expression in neoplastic human endometrial cells. Our data support the hypothesis that the oncogenic effect of estrogens on human endometrial cells may be partially mediated by its effect on the expression of the c-erbB2 proto-oncogene. The finding that glucocorticoids may induce endometrial c-erbB2 gene expression suggests that they may participate in the emergence of uterine neoplasias.
Markogiannakis
E
E
Department of Pharmacology, Medical School and University Hospital, University of Crete, Iraklion, Greece.
Georgoulias
V
V
Margioris
A N
AN
Zoumakis
E
E
Stournaras
C
C
Gravanis
A
A
D000230:Adenocarcinoma / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D003907:Dexamethasone; D004967:Estrogens; D005938:Glucocorticoids; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; C000715470:MAS1 protein, human; C016601:afimoxifene