Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to elucidate the mechanism by which c-myc and transforming growth factor-alpha (TGF-alpha) cooperate in hepatocyte tumor development, we have analyzed signaling by the epidermal growth factor (EGF) receptor and the consequent regulation of receptor number in transgenic mice bearing the c-myc transgene under the control of the albumin enhancer/promoter. 125I-EGF binding and Scatchard analysis indicated a single class of high affinity receptors with the total number of binding sites of 1.2 X 10(4) +/- 600 and 2.5 X 10(5) +/- 1000 sites/cell in the normal and c-myc hepatocytes in primary culture, respectively. After 72 h of EGF exposure in culture, the number of detectable EGF receptors on the cell surface of the c-myc hepatocytes was not reduced, whereas the number of EGF receptors on normal hepatocytes was reduced to 32% that of untreated hepatocytes. Nuclear run-on experiments done with nuclei isolated from intact livers demonstrated that transcription of the EGF receptor was 4.9-fold higher in c-myc mice. Increased levels of the transcriptional factor SP1 in the c-myc hepatocytes in vivo and in primary culture, suggest a mechanism for the increased transcription of the EGF receptor. c-myc also increases the expression of TGF-alpha; a consequent increase in tyrosine phosphorylation is also detected in vivo. Thus, the increased number of EGF receptors in c-myc expressing hepatocytes, even after prolonged exposure to EGF, or TGF-alpha in vivo, may allow greater triggering of the EGF receptor signaling cascade.
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PMID:Aberrant expression and regulation of hepatic epidermal growth factor receptor in a c-myc transgenic mouse model. 909 14

The c-erbB-2 gene is frequently overexpressed in human breast cancers as a result of gene amplification and/or elevated transcription. We therefore examined a possible usage of promoter regions of the c-erbB-2 gene to express a suicide gene preferentially in breast cancer cells. Previous studies did not reveal the minimal promoter region that enabled transcriptional activation specific to breast cancer cells. The present reporter gene assays using deletion mutants of the c-erbB-2 promoter region demonstrated that the 251-bp (-213/+38 from the transcriptional start site), but not the 125-bp, fragment (-87/+38) could direct transcription of the linked luciferase gene better than the SV40 immediate early promoter in breast cancer cells. In contrast, the 251-bp fragment-mediated promoter activity in nonbreast cancer cells and in normal fibroblasts was lower than the activity by the SV40 promoter. The 126-bp fragment (-213/-87) thereby contains a cis-acting element(s), which is responsible for the preferential transcriptional activity in breast cancer cells. An electrophoretic mobility shift assay suggested that a possible modification of a transcriptional factor was involved in the tumor specificity. Transfection with the plasmid DNA containing the herpes simplex virus thymidine kinase gene linked with the 251-bp promoter (p256-TK) resulted in increased sensitivity to ganciclovir in breast cancer, but not in nonbreast cancer cells. Administration of ganciclovir into nude mice bearing human breast tumors that were transfected with the p256-TK DNA suppressed subsequent growth of the transplanted tumors. These results suggest that delivery of a suicide gene linked with the 251-bp c-erbB-2 promoter can be a feasible therapeutic strategy specific to breast cancer.
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PMID:A minimum c-erbB-2 promoter-mediated expression of herpes simplex virus thymidine kinase gene confers selective cytotoxicity of human breast cancer cells to ganciclovir. 1177 79