Quantitative variation of proto-oncogene and cytokine gene expression in isolated breast fibroblasts.
Transcripts coding for transcription factors (RB, P53, FOS, MYC, MYB, ERBA, REL), growth factors (FGF1, FGF2, INT2, TGFA, TGFB, PDGF, IGF1, IGF2), interleukins, (IL1, IL2, IL3, IL4, IL6, TNF), growth-factor receptors or cytosolic protein kinases (RAF, PIM, FES, MET, SRC, ROS, TRK, KIT, CSFR, IGFR, PDGFR, EGFR, NEU) were quantified in cultured human mammary fibroblasts from normal tissues, benign tumours, carcinomas and post-radiation fibrosis lesions by slot-blot autoradiography and image analysis. The effects of a differentiating agent (cholera toxin) and of a tumour promoter (12-O-tetradecanoyl-phorbol-13-acetate) were also examined. The drugs modulated the levels of the anti-oncogene transcripts (RB, P53) and of ERBA, REL, RAF, MET, ROS, TRK, CSFR, EGFR, NEU, FGF1, INT2, IGF1, IL1, IL2, IL4 and IL6. Apart from this variation, there were multiple differences in gene expression among normal and pathological cells (concerning all but P53, TGFB and interleukin transcripts) and between sub-types defined by the presence of alpha-sm-actin (myofibroblasts) or EDB-fibronectin (RAF, ROS, FES, KIT, IGFR, NEU, INT2, TGFB, PDGF, IGFs, ILs). It appears, therefore, that mammary stroma progress irreversibly along with the epithelium during tumoral development, and that breast cancer is not only a multi-gene but also a multi-tissue phenotype.
Spanakis
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E
Institut d'Oncologie Cellulaire et Moléculaire Humaine, Bobigny, France.
Brouty-Boyé
D
D
D001940:Breast / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002455:Cell Division; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006133:Growth Substances; D007378:Interleukins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate