E-cadherin transfection down-regulates the epidermal growth factor receptor and reverses the invasive phenotype of human papilloma virus- transfected keratinocytes

Jonathan Wilding, Karen H. Vousden, W. Patrick Soutter, Pierre D. McCrea, Raffael Del Buono, Massimo Pignatelli

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The human papillomavirus type 16 (HPV-16), the type most often associated with cervical cancer, immortalizes primary keratinocytes and inhibits serum/calcium-stimulated differentiation in culture. In this study, we have used a model of keratinocyte immortalization based upon HPV-16 to analyze perturbation of function and expression of E-cadherin, a Ca2+- dependent cell-cell adhesion molecule expressed by normal keratinocytes, and its associated proteins. An immortalized keratinocyte cell line generated by cotransfection with HPV-16 E6 and E7 showed decreased membrane E-cadherin expression and redistribution of α-, β-, and γ-catenin from the undercoat membrane to the cytoplasm. No changes in the level of expression were seen. Selection of the immortalized keratinocyte cell line for resistance to differentiation generated a more transformed cell line with an invasive phenotype, down-regulated E-cadherin and α-catenin, and up-regulated the epidermal growth factor receptor (EGFr). Transfection of an E-cadherin expression construct into the differentiation-resistant cell line restored membrane-bound E-cadherin and catenin expression, down-regulated the EGFr, and reversed the invasive phenotype. These results indicate that overexpression of the EGFr correlates with perturbation of the E- cadherin/catenin complex seen in the HPV-16 E6- and E7-transfected keratinocytes and may underlie a functional interaction between growth- regulatory factors and adhesion molecules (E-cadherin/catenin).

Original languageEnglish
Pages (from-to)5285-5292
Number of pages8
JournalCancer Research
Volume56
Issue number22
Publication statusPublished - Nov 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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