Erb-B2 homodimerization inhibits MUC1 transcription in cultured human mammary epithelial cells.
MUC1 mucin is a heavily O-glycosylated transmembrane protein that is aberrantly expressed in many carcinomas, including breast cancer. In the present study, the effect of signaling generated from the Erb-B2 homodimer as a result of transcription of the MUC1 gene was investigated in human mammary epithelial cell lines (MTSV1-7 and Hb2) stably transfected with a pBAT/trk-neu construct in which the extracellular domain of Erb-B2 was replaced with the corresponding domain from the nerve growth factor (NGF) receptor. In this system, NGF stimulated homodimerization of Erb-B2 and phosphorylation of its intracellular domain. MTSV1-7/trk-neu and Hb2/trk-neu cells were transiently transfected with a construct in which the MUC1 promoter caused expression of a CAT reporter gene, and were then treated with NGF. These studies showed that MUC1 expression was inhibited by NGF treatment in both cell lines, suggesting that its expression can be regulated by signals resulting from the homodimerization of Erb-B2.
Canbay
Emel
E
Department of General Surgery, Faculty of Medicine, Cumhuriyet University, Sivas 58140, Turkey. canbay@cumhuriyet@.edu.tr
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D019281:Dimerization; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D005809:Genes, Regulator / Q000187:drug effects / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism*; D018396:Mucin-1 / Q000096:biosynthesis* / Q000235:genetics*; D020932:Nerve Growth Factor / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014162:Transfection
D018396:Mucin-1; D020932:Nerve Growth Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D020800:Receptor, Nerve Growth Factor