Counteraction of estradiol‐induced activation of tissue‐type plasminogen activator in a human breast cancer cell line by an anti‐estrogen, LY117018

Abstract

LY117018 is a non-steroid anti-estrogen which exhibits about 100 times higher affinity for estrogen receptor than tamoxifen, another anti-estrogen. The cell line ES-1, which was isolated from human breast cancer MCF-7 cells, was highly sensitive to the cytocidal action of estradiol. Growth of ES-1 cells was inhibited by 10(-8)M 17 beta-estradiol, a concentration that stimulated the growth of parental MCF-7 cells. The estradiol-induced growth inhibition of ES-1 cells was almost completely reversed by treatment with LY117018, but not by treatment with tamoxifen. The relative binding affinity of LY117018 for estradiol receptor was equal to that of estradiol in both MCF-7 and ES-1 cells. Treatment of ES-1 cells with estradiol specifically induced tissue-type plasminogen activator (t-PA), whereas such estradiol-induced activation was not observed in parental MCF-7 cells. Quantitative immunoreactive assays and Northern blot analysis showed that estradiol-induced expression of t-PA was blocked by LY117018 in ES-1 cells. The inhibitory effect of tamoxifen was about 100 times lower than that of LY117018. The inhibition of t-PA gene expression by LY117018 might be due to competitive inhibition with estradiol in estradiol receptor binding.

17β-Estradiol Induces Down-Regulation of Cap43/NDRG1/Drg-1, a Putative Differentiation-Related and Metastasis Suppressor Gene, in Human Breast Cancer Cells

“…We used an E 2 -depleted culture condition to examine whether the addition of E 2 to the five breast cancer cell lines tested in this experiment promoted E 2 -dependent growth. Previous studies have shown that the growth of human breast cancer cell lines depends on the presence of 10 À8 to 10 À9 mol/L E 2 in the culture medium (23,24). Of the five cell lines, the addition of 10 À8 mol/L E 2 enhanced growth in the ER-a-positive cell lines (T47D, MCF-7, and R-27).…”

Breast cancer prognosis is poor when total plasminogen activator activity is low

“…This may be related to the fact that t-PA is an estrogen-inducible enzyme and that is present when the total PA activity is high (Dickermann et al, 1989;Mizoguchi et al, 1990;Uchiumi et al, 1991;Yamashita et al, 1992). The presence of the ER itself in breast cancer is generally thought to be associated with a good prognosis (Foekens et al, 1989), although in our study the prognostic value of ER (P = 0.075) and PgR (P = 0.06) only approached significance (Table IV).…”

The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors

“…The cells were then cultured for 24 hr in RPMI 1640 methioninefree medium containing no serum (2 mlidish), and pulsed for 4 hr with 35S methionine (50 p Ciiml). The labelled, conditioned medium was collected and used for the experiments on EGF-inducible protein secretion or stored at -20°C as described previously (Mizoguchi et al, 1990;Uchiumi et al, 1991). The labelled, conditioned medium was mixed with a % volume of buffer containing 12.5% P-mercaptoethanol, 5% SDS, 25% glycerol and 0 .…”

“…Northern blot analysis was performed as described previously (Mizoguchi et al, 1990;Mawatari et al, 1991;Uchiumi et al, 1991). Total cellular RNA was isolated from tumors or IMC cells incubated with or without EGF.…”