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Tamoxifen resistance in breast cancer cells is accompanied by an enhanced motile and invasive phenotype: inhibition by gefitinib ('Iressa', ZD1839)

Hiscox, Stephen Edward ORCID:, Morgan, Liam David ORCID:, Barrow, Denise, Dutkowski, Carol Mary, Wakeling, Alan and Nicholson, Robert Ian 2004. Tamoxifen resistance in breast cancer cells is accompanied by an enhanced motile and invasive phenotype: inhibition by gefitinib ('Iressa', ZD1839). Clinical & Experimental Metastasis 21 (3) , pp. 201-212. 10.1023/B:CLIN.0000037697.76011.1d

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Despite an initial response to antihormonal therapies, the development of resistance will occur in a significant number of breast cancer patients. The mechanisms that underlie acquired resistance are not yet clear. Using a previously established in vitro cell model of tamoxifen resistance in MCF7 cells, shown to display autocrine epidermal growth factor receptor (EGFR) signalling, we assessed how resistance might modulate their metastatic phenotype in vitro, as metastatic disease is the single most important factor affecting the mortality of cancer patients. Furthermore, we investigated the effect of the EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib (`Iressa', ZD1839; AstraZeneca), on this behaviour. The acquisition of tamoxifen resistance in MCF7 cells was accompanied by a dramatic and significant increase in their invasive and motile nature. The affinity of these cells for matrix components was also enhanced. Inhibition of EGFR signalling with gefitinib reduced both basal and TGF-α-stimulated invasion and motility and reduced cell-matrix adhesion. In conclusion, we demonstrate here that resistance to tamoxifen in breast cancer cells is accompanied by a significant increase in their basal motile and invasive activity, properties associated with increased metastatic potential. Inhibition of EGFR signalling by gefitinib significantly inhibited cell motility and invasion thus suggesting a role for the EGF receptor in the aggressive phenotype of tamoxifen-resistant breast cancer cells. Abbreviations: EGFR – epidermal growth factor receptor; MAPK – mitogen activated protein kinase; TGFα– tumour growth factor α

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Uncontrolled Keywords: breast cancer ; EGFR ; invasion ; endocrine resistance ; motility
Publisher: Kluwer
ISSN: 0262-0898
Last Modified: 03 Feb 2023 02:06

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