Abstract

A number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol. MCF-7 cells were treated with growth factors in the presence and absence of oestradiol. Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and basic fibroblast growth factor (bFGF). Platelet derived growth factor (PDGF) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-beta slightly reduced the stimulation by oestradiol. In the absence of oestradiol, there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive. In the presence of oestradiol, the effects of bFGF and TGF-alpha were additive whereas bFGF acted as an IGF-I antagonist. Overall, bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin. The effects of oestradiol on the sensitivity of cells to the proliferative effects of bFGF did not appear to result from regulation of bFGF receptor expression.

Highlights

  • Transforming growth factors (TGFs), insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), platelet derived growth factor (PDGF) and epidermal growth factor (EGF) as well as other proteins such as cathepsin D have all been implicated in the control of breast cancer cell proliferation

  • We have reported that oestrogens sensitise breast cancer cells to the proliferative effects of IGFs (Stewart et al, 1990) demonstrating that steroids can modulate the response of breast cancer cells to growth factors

  • In the first series of experiments, growth factors which have been implicated in the control of breast cancer cell proliferation were tested for their ability to stimulate the proliferation of MCF-7 cells in the absence and presence of oestradiol

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Summary

Introduction

Transforming growth factors (TGFs), insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), platelet derived growth factor (PDGF) and epidermal growth factor (EGF) as well as other proteins such as cathepsin D have all been implicated in the control of breast cancer cell proliferation Some of these growth factors, such as PDGF, are thought to be synthesised by tumour cells but to influence breast cancer cell proliferation indirectly by regulating the synthesis of other growth factors in stromal cells (Bronzert et al, 1987). Regulation of the synthesis of autocrine growth factors such as TGF-a (Bates et al, 1988) and TGF-,B (Knabbe et al, 1987) by oestrogens and antioestrogens has been reported and may contribute to mediating the effects of oestrogens on breast cancer cell proliferation.

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