title: Decrease of c-erbB-2 and c-myc RNA levels in tamoxifen-treated breast cancer.
abstract: 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.
authors.affiliation: INSERM Unité Hormones et Cancer (U148), Montpellier, France.
authors.forename: X
authors.initials: X
authors.lastname: Le Roy
authors.forename: C
authors.initials: C
authors.lastname: Escot
authors.forename: J P
authors.initials: JP
authors.lastname: Brouillet
authors.forename: C
authors.initials: C
authors.lastname: Theillet
authors.forename: T
authors.initials: T
authors.lastname: Maudelonde
authors.forename: J
authors.initials: J
authors.lastname: Simony-Lafontaine
authors.forename: H
authors.initials: H
authors.lastname: Pujol
authors.forename: H
authors.initials: H
authors.lastname: Rochefort
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics*; D015342:DNA Probes; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D015513:Oncogene Proteins / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012313:RNA / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D015342:DNA Probes; D004958:Estradiol; D004965:Estrogen Antagonists; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors; D006133:Growth Substances; D015513:Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C496444:FGF3 protein, human; C496445:FGF4 protein, human