Transfection of anti-sense complementary DNA of human epidermal-growth- factor receptor attenuates the proliferation of human non-small-cell-lung- cancer cells

Kang Fang, Mei Hui Chen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The proliferation of human non-small-cell-lung-cancer (NSCLC) cells is regulated by the epidermal-growth-factor-receptor (EGFR)-mediated autocrine loop that interacts with transforming growth factor-α (TGF-α) of autocrine or paracrine origin. We have shown that EGFR expression is elevated in the brain metastatic variant of human NSCLC cells H226Br, which thereby acquire their increased sensitivity toward exogenous TGF-α. To determine detailed cell-phenotype changes as a result of EGFR down-regulation, H226Br cells were transfected with a human EGFR-cDNA construct encompassing an N-terminal fragment (1.8 kb) in anti-sense orientation downstream of the cytomegalovirus (CMV) promoter. The EG FR transcript expressed in the 3'-5' direction is expected to neutralize EGFR mRNA and to reduce protein expression correspondingly. The established cell lines resistant to G418 were shown integrated with the transfected construct and their proliferation rates reduced as compared with the parental cells and with those transfected with vector alone. Down-regulated EGFR expression in cells with the anti-sense construct can be confirmed by Scatchard analysis and suppressed EGFR kinase activity. The restrained-growth phenotype is also demonstrated in the prolonged G2-M phase during the cell cycle, and correlated with impairment of cell proliferation. This finding suggests that EGFR over-expression is critical in maintaining the malignant phenotype of NSCLC cells, thereby providing a valuable biomarker and potential target prevention for lung- cancer-cell proliferation.

Original languageEnglish
Pages (from-to)471-478
Number of pages8
JournalInternational Journal of Cancer
Volume81
Issue number3
Publication statusPublished - 1999 Apr 19

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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