Decrease of c-erbB-2 and c-myc RNA levels in tamoxifen-treated breast cancer

Oncogene. 1991 Mar;6(3):431-7.


The c-myc, c-erbB-2, hst and int-2 oncogenes are frequently amplified and/or overexpressed in human breast carcinomas. We studied the effect of tamoxifen on RNA levels of these oncogenes in 19 breast cancer patients treated for 3 weeks prior to surgery as compared with 22 control patients. RNA levels were measured by in situ hybridization coupled with computer-aided quantification. c-myc and c-erbB-2 expression was high in the control population (mean values: 23.4 and 29.1 grains/cell respectively) and significantly decreased in the tamoxifen-treated population (mean values: 14.6 and 7.4 grains/cell respectively) (P = 0.018, P = 0.003 respectively); hst and int-2 RNA levels were low (2-6 grains/cell) and not significantly altered by the treatment. There was a correlation between gene amplification and expression for c-erbB-2 (P = 0.0005) and hst (P = 0.02) in the control population. Elevated c-erbB-2 RNA level was correlated with the absence of estrogen (P = 0.02) or progesterone (P = 0.05) receptors. In the ER+ population, the tamoxifen-treated group had significantly lower c-myc expression levels than the control group (P = 0.04) which is in agreement with the estrogen induction of c-myc in ER+ T47D cell line and its inhibition by antiestrogens. Surprisingly, c-erbB-2 expression in the tamoxifen-treated group was significantly diminished in the ER- (P = 0.02) and PR- (P = 0.01) populations. This effect was not observed in the ER- BT474 cell line. These results suggest that in vivo tamoxifen decreases c-myc and c-erbB-2 RNA levels in breast cancer cells via two different mechanisms. To our knowledge this is the first evidence of in vivo down regulation of a gene by tamoxifen in ER- breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy
  • Carcinoma, Intraductal, Noninfiltrating / genetics*
  • DNA Probes
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / genetics*
  • Gene Expression Regulation
  • Growth Substances / genetics*
  • Humans
  • Middle Aged
  • Nucleic Acid Hybridization
  • Oncogene Proteins / genetics*
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA / analysis*
  • Receptor, ErbB-2
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Tamoxifen / therapeutic use*


  • DNA Probes
  • Estrogen Antagonists
  • FGF3 protein, human
  • FGF4 protein, human
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factor 4
  • Growth Substances
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • Estradiol
  • Fibroblast Growth Factors
  • RNA
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2