Three-dimensional extracellular matrix culture models of EGFR signalling and drug response

P. A. Kenny

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Three-dimensional extracellular matrix culture, on substrata such as Matrigel, restores many aspects of the differentiated state to non-malignant cells from a variety of tissues. We have adapted these techniques to study EGFR (epidermal growth factor receptor) signalling and drug response in breast cancer cell lines. EGFR-dependent breast cancer cell lines undergo a striking reversion of the malignant phenotype upon treatment with inhibitors targeting the receptor, or downstream signalling intermediates such as mitogen-activated protein kinase and PI3K (phosphoinositide 3-kinase). Using this approach, we have recently reported that EGFR signalling in breast cancer can be effectively inhibited by blocking the activity of a key protease, TACE [TNFα (tumour necrosis factor α)-converting enzyme], which regulates the bioavailability of EGFR ligands. These results suggest a new way to target EGFR signalling in tumours of the breast and other epithelial tissues and underline the value of three-dimensional extracellular matrix culture models for exploring cancer-relevant signalling processes ex vivo.

Original languageEnglish (US)
Pages (from-to)665-668
Number of pages4
JournalBiochemical Society transactions
Volume35
Issue number4
DOIs
StatePublished - Aug 2007

Keywords

  • Breast cancer cell line
  • Drug response
  • Epidermal growth factor receptor (EGFR)
  • Three-dimensional extracellular matrix culture
  • Tumour necrosis factor α (TNFα)
  • Tumour necrosis factor α-converting enzyme (TACE)

ASJC Scopus subject areas

  • Biochemistry

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