Factors modulating integrin Beta I expression on the breast cancer cell lines MCF-7 and MDA-MB-231

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The metastatic cascade describes a sequence of cellular events that forms the pathological basis of tumour progression. The integrins are cell adhesion molecules that play a leading role in this complex process. The objective of this study is to improve our understanding of the role of integrins in breast cancer metastasis by investigating how growth factors (Epidermal Growth Factor (EGF) and Insulin-like Growth Factor 1 (IGF-1)), oestradiol (E2) and tamoxifen affect integrin β I expression. The breast cancer cell lines MCF-7 and MDA-MB-231 were used and integrin expression measured by Western Blotting.

We have demonstrated that EGF and IGF-1 up-regulate integrin β I expression on the MDA-MB-231 cell line by 2.7- and 2.8-fold respectively. By doing so these cells may generally become more adhesive and therefore less prone to metastasise. Tamoxifen down-regulated integrin β I expression on this oestrogen receptor (ER)-negative cell line, with maximal effect at 10^-6 M (34% reduction). This suggests signalling through an alternative pathway. Integrin down-regulation may render cells less adhesive and therefore less invasive.

High concentrations of E2 significantly up-regulated integrin β I expression on the MCF-7 cell line, whereas low concentrations resulted in a down-regulation, with maximal effects at 10^-7 M (1.7-fold induction) and 10^-11 M (29% reduction) respectively. Conversely, high concentrations of tamoxifen down-regulated integrin β I expression and low concentrations up-regulated expression, with maximal effects at 10^-8M (49% reduction) and 10^-9 M (2.7-fold induction) respectively. These data provide a cellular basis for the modulation of integrin expression and may explain why some ER-negative patients respond well to tamoxifen. Identification of factors that regulate integrin expression may lead to the development of novel anti-metastatic agents.