Antisense oligonucleotides to the epidermal growth factor receptor

Lois Witters, Rakesh Kumar, Mahitosh Mandal, C. Frank Bennett, Loren Miraglia, Allan Lipton

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Overexpression of the epidermal growth factor receptor (EGFR) has been observed in human breast tumors and is associated with poor prognosis in breast cancer patients. This would suggest that blocking the activity of the EGFR is a logical approach in the treatment of breast cancer. Three 20-mer phosphorothioate oligodeoxynucleotides were designed to target different regions of the human epidermal growth factor receptor (EGFR) mRNA. Several analogs of these oligodeoxynucleotides (the 2'-fluoro analog, the 2'-propoxy analog, and/or the 5-methyl cytosine analog) were also evaluated. We added these compounds to a human ovarian carcinoma cell line (SKOV3) and a human lung carcinoma line (A549), both of which overexpress the EGFR. All of these antisense oligonucleotides inhibited expression of the 10 kb EGFR mRNA (range: 22-97% inhibition) compared to a scrambled control oligonucleotide or an untreated control. Expression of the less prominent 5.6 kb EGFR mRNA band was also inhibited by all but two of the parent oligonucleotides. No inhibition of this 5.6 kb band was found with the control oligonucleotide. The reduction in the expression of EGFR mRNA by the three most potent antisense compounds was accompanied by a significant reduction of EGFR protein (90-98%) and in vitro growth inhibition of SKOV3 cells as compared to the control oligonucleotide.

Original languageEnglish (US)
Pages (from-to)41-50
Number of pages10
JournalBreast Cancer Research and Treatment
Volume53
Issue number1
DOIs
StatePublished - Mar 22 1999

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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