Modulation of EGF receptor protooncogene expression by growth factors and hormones in human breast carcinoma cells.
In this review I summarize the experimental data in favor of the notion that control of epidermal growth factor (EGF) receptor (R) and/or c-erbB-2 protooncogene expression by specific autocrine growth factors and certain classical endocrine hormones serves as a transducer of extracellular signals that ultimately lead to growth responses in breast carcinoma cells. I summarize some new results on the role of epidermal growth factor (EGF), transforming growth factor (TGF) alpha, and TGF beta in the control of EGF-R protooncogene expression in human breast carcinoma cells. Furthermore, the data embracing the hypothesis that the growth actions of hormone receptors that are homologous to the v-erbA oncogene (estrogens, progesterone, thyroid hormones, retinoic acid, and vitamin D) are mediated, in part, by modulating EGF-R and/or c-erbB-2 protooncogene transcription are reviewed. Finally, I develop the theme that cooperation of certain c-erb-A-related, c-erbB-2 and/or EGF-R gene products contribute to the uncontrolled growth of human mammary carcinoma cells. From the evidence reviewed, one can infer that elucidation of the molecular control of EGF-R/c-erbB-2 gene expression by c-erbA-related gene products may lead to both a better understanding of breast carcinogenesis and a new therapeutic approach directed at controlling the transcriptional responses of EGF-R/c-erbB-2 genes.
Laboratory of Molecular Oncology, Veterans Administration Medical Center, St. Louis, MO 63106.
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Fernandez-Pol
D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D002762:Cholecalciferol / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology; D011374:Progesterone / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D014408:Biomarkers, Tumor; D002762:Cholecalciferol; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D004967:Estrogens; D006854:Hydrocortisone; D011374:Progesterone; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D014284:Triiodothyronine