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 t he Ishikawa endometrial cell line as well as in human endometrial aden ocarcinoma cells. Both cell types express the 4.6 and 2.3 kb c-erbB2 m RNAs. Estradiol significantly increased in a time-and dose-dependent m anner the content of c-erbB2 mRNA and the concentration of NEU protein in Ishikawa cell extracts, while progesterone was devoid of any activ ity. The effect of estradiol was partially reversed by the antiestroge n 4-hydroxytamoxifen, which, however, given alone exhibited agonist ef fects. Glucocorticoid dexamethasone augmented in a time-and dose-depen dent 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 ou r knowledge, this is the first report documenting the induction by ste roid hormones of c-erbB2 gene expression in neoplastic human endometri al 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 t hat glucocorticoids may induce endometrial c-erbB2 gene expression sug gests that they may participate in the emergence of uterine neoplasias .