SKOV3 OVARIAN-CARCINOMA CELLS HAVE FUNCTIONAL ESTROGEN-RECEPTOR BUT ARE GROWTH-RESISTANT TO ESTROGEN AND ANTIESTROGENS

Estrogen receptor positive ovarian cancer is often refractile to antie strogen therapy. Here we describe the SKOV3 human ovarian carcinoma ce ll line as an in vitro model for estrogen and antiestrogen resistant o varian cancer. While SKOV3 cells expressed estrogen receptor (ER) mRNA and protein at a similar level as the estrogen responsive T47D breast carcinoma cell line, their growth was not responsive to estradiol (E( 2)) and was not inhibited by the antiestrogens OH-tamoxifen and ICI 16 4,384. The ER in SKOV3 cells was normal with respect to apparent K-d f or binding with E(2), E(2) regulation of a transiently transfected ERE driven reporter gene, and E(2) stimulation of expression of the early growth response genes c-myc and c-fos. However, the SKOV3 cells exhib ited no expression of the progesterone receptor gene (PR) even after a ddition of E(2), and the protein products of the estrogen responsive g enes HER-2/neu and cathepsin D were expressed at constitutive levels t hat were not regulated by E(2). Therefore, estrogen resistance in thes e cells may be a result of constitutive expression and loss of E(2) re gulation of selected growth regulatory gene products rather than a def ect in estrogen activation of ER as a transcriptional regulator.