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)

Gene amplification (overexpression) of c-erb B-2 was tested in a variety of cystic renal diseases, renal cell neoplasms (adenomas and carcinomas) and end stage kidneys without cysts. C-erb B-2 encodes a receptor-like protein that shares homology with, but is distinct from the epidermal growth factor (EGF) receptor. A monoclonal antibody that immunoprecipitates a protein of approximately 185 kD from a lysate of NIH/3T3 cells transfected with the c-erb B-2 gene was utilized for testing. Simple renal cysts, cystic renal dysplasia, autosomal recessive polycystic kidney disease (ARPKD), and non-cystic, essentially normal kidneys failed to show c-erb B-2 overexpression. In contrast, autosomal-dominant polycystic kidney disease (ADPKD), acquired (dialysis-associated) cystic disease (ACD), non-cystic end stage kidneys and renal cell neoplasms revealed overexpression of c-erb B-2 with some frequency (40% or more of cases tested). Three cystic disorders revealing c-erb B-2 overexpression also showed platelet-derived growth factors (PDGFs) expression in similar locations (cyst lining and adjacent tubules). Other growth factors [insulin-like growth factor (IGF-I), fibroblast growth factor (FGF) and beta transforming growth factor (TGF beta)] were not noted to be overexpressed in either c-erb B-2 positive or negative cystic diseases. C-erb B-2 may be a marker related to the proliferative/growth capabilities of selected cystic diseases, including potential for associated genesis of benign and malignant renal cell tumors.
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PMID:C-erb B-2 amplification in cystic renal disease. 168 89

Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression of antigen Exo-1 is associated with hyperproliferation in an epithelial tissue compartment composed of cells which have not yet reached their terminal differentiation state. Increased amounts of mRNA of the growth factor receptor system of epidermal growth factor (EGF) receptor and its ligand transforming growth factor (TGF)-alpha were associated with the malignant phenotype of RCC. Increased expression of EGF receptor and TGF-alpha, although less prominent, were also observed in polycystic kidney cells compared with normal kidney cells. In conclusion, the expression of Exo-1 in cyst-lining epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) and the altered regulation of TGF-alpha and EGF receptor in these cells contribute to the hypothesis that hyperproliferation is an underlying pathogenic mechanism of ADPKD.
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PMID:Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma. 173 78

The effect of various regimens of treatment with melatonin on the development of mammary tumors in HER2/neu transgenic mice was investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen and as given melatonin with tap water (20 mg/l) during the night time 5 times monthly (interrupted treatments) or constantly to natural death. Intact mice served as controls. Treatment with melatonin slowed down age-related disturbances in estrous function most in the group exposed to interrupted treatment with the hormone. Constant treatment with melatonin decreased incidence and size of mammary adenocarcinomas, and incidence of lung metastases, compared to controls. The number of mice bearing 4 and more tumors was reduced in the group with constant melatonin treatment. Interrupted treatment with melatonin promote mammary carcinogenesis in HER-2/neu transgenic mice. The data demonstrate the regimen-dependent inhibitory effect of melatonin on the development of spontaneous mammary tumors in HER-2/neu mice but not on overall survival with implication about the likely cause of the effect. Polycystic kidney disease is common in this transgenic line. Adverse effect of melatonin on the life span in our study may be unique to the transgenic model used and may not be relevant to the suppressive effect of melatonin in delay of mammary cancer.
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PMID:The effect of melatonin treatment regimen on mammary adenocarcinoma development in HER-2/neu transgenic mice. 1247 12

The pathogenesis of polycystic liver disease is not well understood. The putative function of the associated proteins, hepatocystin and Sec63p, do not give insight in their role in cystogenesis and their tissue-wide expression does not fit with the liver-specific phenotype of the disease. We designed this study with the specific aim to dissect whether pathways involved in polycystic kidney diseases are also implicated in polycystic liver disease. Therefore, we immunohistochemically stained cyst tissue specimen with antibodies directed against markers for apoptosis, proliferation, growth receptors, signaling and adhesion. We analyzed genotyped polycystic liver disease cyst tissue (n=21) compared with normal liver tissue (n=13). None of the cysts showed proliferation of epithelial cells. In addition, anti-apoptosis marker Bcl-2 revealed slight increase in expression, with variable increase of apoptosis marker active caspase 3. Growth factor receptors, EGFR and c-erbB-2, were overexpressed and mislocalized. We found EGFR staining in the nuclei of cyst epithelial cells regardless of mutational state of the patient. Further, in hepatocystin-mutant polycystic liver disease patients, apical membranous staining of c-erbB-2 and adhesion markers, MUC1 and CEA, was lost and the proteins appeared to be retained in cytoplasm of cyst epithelia. Finally, we found loss of adhesion molecules E-cadherin and Ep-CAM in cyst epithelium of all patients. Nevertheless, we observed normal beta-catenin expression. Our results show that polycystic liver disease cystogenesis is different from renal cystogenesis. Polycystic liver disease involves overexpression of growth factor receptors and loss of adhesion. In contrast, proliferation or deregulated apoptosis do not seem to be implicated. Moreover differential findings for PRKCSH- and SEC63-associated polycystic liver disease suggest a divergent mechanism for cystogenesis in these two groups.
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PMID:Disrupted cell adhesion but not proliferation mediates cyst formation in polycystic liver disease. 1858 25