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 presence of estrogen receptors (ERs), as detected by immunohistochemistry (IHC), is a weak prognostic marker of clinical outcome in breast cancer, but a strong predictive marker for response, for example, to tamoxifen-based therapy. As with all IHC markers, factors such as tissue fixation (both type and duration), the choice of antibody, and the threshold for interpretation of positive immunostaining can dramatically affect test accuracy and reproducibility. For example, optimal fixation for detection of ER requires at least 6-8 h in formalin, and the use of newer antibodies such as SP1 may identify additional patients who might benefit from hormonal therapy. Although the threshold for positivity may be as few as 1% of tumor cells showing nuclear signal, recent studies appear to demonstrate a dichotomization of ER IHC, with the vast majority of cases showing all positive or all negative results. This may be helpful in dictating the appropriateness of hormonal therapy, but quantification of ER by IHC, or other methods, may play a more important role in the future. Breast cancers with human epidermal receptor protein-2 (c-erbB-2; HER2) alterations are critical to identify because such tumors require unique treatment, including the use of targeted therapies such as trastuzumab. HER2 alterations at the DNA (amplification) and protein (overexpression) level usually occur in concert, and both fluorescence in situ hybridization (FISH) or IHC can be accurate methods to assess these alterations. However, recent studies have suggested that serious reproducibility issues exist in both FISH and IHC HER2 studies. To address this, a joint committee of both the American Society for Clinical Oncologists and the College of American Pathologists has promulgated new guidelines for HER2 testing. These include the following: (a) recommendations for tissue fixation for more than 6 and less than 48 h; (b) new scoring criteria, including a new threshold of 30% strong immunostaining for classification of 3+; (c) introduction of the term 'equivocal' to characterize HER2 studies that are 2+ by IHC and/or show HER2/chromosome 17 ratios of between 1.8 and 2.2 by FISH; (d) requirements for laboratories to validate HER2 assays, generally through the cross-testing of cases with another HER2 methodology, with laboratories required to attain 95% concordance for both positive and negative tests; (e) participation in HER2 proficiency testing.
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PMID:Current issues in ER and HER2 testing by IHC in breast cancer. 1843 74