Correlation between hormone dependency and the regulation of epidermal growth factor receptor by tumor promoters in human mammary carcinoma cells.

Abstract

The effects of the tumor promoter phorbol 12-tetradecanoate 13-acetate (TPA) on the epidermal growth factor (EGF) receptor levels were investigated in hormonedependent (MCF-7, T-47-D, and ZR-75-1) and hormoneindependent (MDA-MB-231, HBL-100, and BT-20) human mammary carcinoma cell lines. In the absence of TPA, hormone-independent cell lines contained high concentrations of low-affinity EGF receptors (apparent Kd = 8 x 1010 M), whereas hormone-dependent cell lines exhibited low concentrations of high-affinity receptors (apparent Kd = 1 x 10-10 M). TPA causes a change of the receptor from a high-to the low-affinity state in hormone-dependent cell lines (MCF-7, T-47-D, and ZR-75-1), as well as in the hormone-independent HBL-100, whereas the affinity remained unchanged in MDA-MB-231 and BT-20 cells. In addition, progesterone receptor levels are decreased after TPA treatment in the hormonedependent cell lines MCF-7, T-47-D, and ZR-75-1, whereas the estrogen receptor levels remained unchanged. Tumor promoters such as TPA or teleocidin inhibited the proliferation of these cell lines at concentrations above 10 ,uM with the exception of the T-47-D cells. The most sensitive cell line towards growth inhibition by tumor promoter was the hormone-dependent MCF-7 cell line. Evaluation of different TPA analogs indicated a positive correlation between the growth-inhibitory effects and their ability to stimulate the subcellular redistribution of protein kinase C activity in MCF-7 cells. These data suggest a protein kinase C-mediated down-regulation of the progesterone receptor concentration and of the EGF receptor affinity, which is supposed to mediate the mitogenic response. Furthermore, these results support the hypothesis that the tumorderived growth factors induced by estradiol act via the EGF receptor in hormone-dependent mammary carcinoma cells.

Epidermal growth factor receptors (EGFR) in human ovarian cancer

“…Secondly it has been shown that there is an interaction between protein kinase C (PKC) and the EGFR such that there is a decrease in affinity for EGF and that high levels of PKC are associated with hormone independent tumours (Wyss et al, 1987). Thirdly it is possible that another growth factor is interacting with PKC, modulating EGFR (Roos et al, 1986). The observed discordance in individual patients may be due to different populations of tumour cells in different sections which have been used for biochemical assay just as there may be variations in histology between sections.…”

Association of PKC δ and active Src in PMA-treated MCF-7 human breast cancer cells

“…Our results additionally show that while the association of Src and PKC d in the C fraction is correlated with the catalytic activity of PKC d in the TS fraction, the activity of PKC d towards the substrate rHSP25 does not require the presence of phosphorylated tyrosine on PKC d. Additional studies are required to determine whether the tyrosine phosphorylation of PKC d is an early event which occurs in vivo in response to PMA prior to the translocation of PKC d and formation of an enzymatically active conformation or whether the tyrosine phosphorylation of PKC d occurs subsequent to membrane activation, perhaps targeting the enzyme for degradation. Since activation of PKC d in various cellular models (Mischak et al, 1993;Watanabe et al, 1992;Mishima et al, 1994;Hirai et al, 1994) and PMA treatment of MCF-7 cells (Roos et al, 1986;Darbon et al, 1986;Issandou et al, 1988) both lead to growth inhibition, it will be very interesting to determine if PMA-dependent Src activation is required for PMA-dependent growth inhibition of MCF-7 breast cancer cells.…”

The combination of epigallocatechin gallate and curcumin suppresses ERα‐breast cancer cell growth in vitro and in vivo

“…8,[32][33][34][35][36] For example, EGCG and green tea extracts were both recently shown to decrease tumor incidence and burden in athymic mice inoculated with MDA-MB-231 (ERa-) human breast cancer cells. 8,36 A potential mechanism for this effect is via inhibition of the epidermal growth factor receptor (EGFR), which is overexpressed in ERa-breast cancer cells 37 and patients. 38 Importantly, EGCG inhibited the activation of the EGFR in MDA-MB-231 breast carcinoma cells, 39 indicating that this may also occur in in vivo xenograft models using this cell line.…”