EGF-related peptides are involved in the proliferation and survival of MDA-MB-468 human breast carcinoma cells

Int J Cancer. 1999 Feb 9;80(4):589-94. doi: 10.1002/(sici)1097-0215(19990209)80:4<589::aid-ijc17>;2-d.


A majority of human breast carcinomas co-express the epidermal growth factor (EGF)-like peptides CRIPTO (CR), amphiregulin (AR) and transforming growth factor alpha (TGF-alpha). MDA-MB-468 breast carcinoma cells express CR, AR and TGFalpha, while SK-BR-3 cells express CR and TGF-alpha. Anti-sense phosphorothioate oligodeoxynucleotides (AS S-oligos) directed against either CR or TGF-alpha inhibit the proliferation of both cell lines. A 40-50% growth inhibition was observed at a 2-microM concentration of each AS S-oligo. Treatment with the AR AS S-oligo also resulted in a significant inhibition of MDA-MB-468 anchorage dependent growth (ADG). No significant growth inhibition was observed when MDA-MB-468 or SK-BR-3 cells were treated with a mis-sense S-oligo. The AS S-oligos inhibited the expression of AR, CR or TGF-alpha proteins and mRNAs, as assessed by immuno-cytochemistry and semi-quantitative RT-PCR. An additive growth-inhibitory effect was observed when MDA-MB-468 cells were treated with a combination of EGF-related AS S-oligos. Indeed, treatment of MDA-MB-468 cells with a combination of AR, CR and TGF-alpha AS S-oligos resulted in about 70% growth inhibition at a concentration of 0.7 microM each. Finally, treatment of MDA-MB-468 cells with a combination either of the 3 AS S-oligos or of an EGF receptor-blocking antibody (MAb 225) and either CR, AR or TGFalpha AS S-oligos resulted in a significant increase in DNA fragmentation. Our data suggest that the EGF-related peptides are involved in the proliferation and survival of breast carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amphiregulin
  • Biomarkers, Tumor / physiology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Division
  • Cell Survival
  • EGF Family of Proteins
  • Epidermal Growth Factor*
  • Female
  • GPI-Linked Proteins
  • Glycoproteins / physiology*
  • Growth Substances / physiology*
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Membrane Glycoproteins*
  • Neoplasm Proteins / physiology*
  • Polymerase Chain Reaction
  • Transforming Growth Factor alpha / physiology*
  • Tumor Cells, Cultured


  • AREG protein, human
  • Amphiregulin
  • Biomarkers, Tumor
  • EGF Family of Proteins
  • GPI-Linked Proteins
  • Glycoproteins
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • TDGF1 protein, human
  • Transforming Growth Factor alpha
  • Epidermal Growth Factor