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)

Computer-assisted image analysis was used to demonstrate in exponentially proliferating human tumor cells the uneven postmitotic apportionment of several oncogene-encoded proteins (ras p21; erbB-2 p185; fos p55; myc p62). This observation may provide the explanation for the high degree of heterogeneity of postmitotic cells and the asynchrony in cell cycle traverse of cultured cells.
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PMID:Asymmetric distribution of oncogene products at mitosis. 135 Jun 77

Monoclonal antibodies to myc, c-erbB-2 and epidermal growth factor-receptor (EGF-R) were raised using a synthetic peptide approach. The antibodies were characterised by ELISA, immunoblotting, immunoprecipitation and immunocytochemical procedures against cognate peptide and native proteins. All of the monoclonal antibodies detected peptide-blockable bands of appropriate molecular weight (myc-p62/66 kDa, c-erbB-2-185kDa; EGF-R-150/170 kDa) on immunoblots. The monoclonal antibodies to c-erbB-2 and EGF-R immunostained subpopulations of tumour cells on sections of formalin-fixed, paraffin wax embedded human infiltrating and invasive ductal carcinomas of breast. Intense blood cell staining was observed with the EGF-R antibody. This staining was shown to be peptide blockable and may reveal a true localisation for the EGF-receptor protein, a closely-related (erbB) protein or a degradation product. The monoclonal antibody to a common peptide from the myc protein family was epitope scanned using a modification of the Geysen pin technique. Hexapeptide sequence Ala-Pro-Ser-Glu-Asp-Ile was found to be bound most strongly by the myc monoclonal antibody, and amino acids Pro2 and Glu4 were found to be essential for antibody binding. The use of synthetic peptides for the production of monoclonal antibodies with predetermined specificity, which may be precisely identified using the epitope scanning technique, is discussed.
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PMID:The production and characterisation of monoclonal antibodies to myc, c-erbB-2 and EFG-receptor using a synthetic peptide approach. 169 66

The use of antibodies permits the study of oncogene product expression in cells and tissues. However, quantitation of the levels of expression in immunohistochemical preparations is beset by difficulties, and the available scoring system provide semiquantitative data at best. Here we describe the use of computer-assisted image analysis for determination of oncoprotein levels in a model system and compare the results with those generated by flow cytometric analysis. The oncogene products measured are located in the nucleus (c-myc p62 and c-fos p55), the inner surface of the membrane (c-ras p21), and both sides of the membrane (c-erbB-2 p185). In each instance, both analytic modalities yielded concordant results. Our data indicate that computer-assisted image analysis is a useful tool for quantitating cell components in immunohistochemical preparations.
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PMID:Quantitation of oncogene products by computer-assisted image analysis and flow cytometry. 196 31

We have studied ras p21, c-myc p62 and c-erbB-2 oncogene expression in fourteen Greek patients with NON AIDS Mediterranean Kaposi's sarcoma using immunohistochemical analysis. Elevated expression of ras p21 expression was observed in all 14 cases studied (8 of which had intense levels of staining), whereas expression of c-myc and c-erbB-2 was less frequent, (6 out of 13 cases tested showed elevated c-myc expression and 6 out of 13 showed elevated c-erbB-2 expression). This report indicates that aberrant ras p21 oncogene expression is a feature of Kaposi's sarcoma and may be important in the early stages of this disease.
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PMID:Ras, C-myc and C-erbB-2 oncoprotein expression in non-AIDS Mediterranean Kaposi's sarcoma. 198 Sep 98

The expression of ras, c-myc and c-erbB-2 oncoproteins in 100 human (73 ductal and 27 lobular) breast carcinomas has been examined using an immunohistochemical analysis. The monoclonal antibody Y13 259 has been used for the ras p21, the monoclonal antibody Myc1-9E10 for the c-myc p62 and the polyclonal antibody pAb1 (from Triton Bioscience Inc.) for the c-erbB-2 p185 oncoproteins. The following conclusions can be drawn from the analysis: Of the 100 breast carcinoma cases studied only 14 did not express any of the three oncogenes. The remaining 86 were positive for one or more of the three oncoproteins. Ductal carcinomas expressed oncoproteins in 92% of the cases (67/73), whereas lobular carcinomas expressed them in 70% of the cases (19/27). The most frequently expressed was c-myc p62 in 70% of cases followed by ras p21, 55% and c-erbB-2, 35%. Elevated expression of ras, myc or erbB-2 oncogenes did not correlate with the presence of metastasis in auxiliary lymph nodes, the numbers of infiltrated lymph nodes the grade of the tumor or hormone status. However, there appears to be a correlation between increased ras staining intensity and patient's age, below 50 years.
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PMID:ras, c-myc and c-erbB-2 oncoproteins in human breast cancer. 257 23

The expression of the proteins encoded by the ras, myc, and erb B-2 oncogenes was examined in 63 paraffin-embedded human cholangiocarcinomas of Thai and English origin using immunohistochemistry. The observed distributions were compared with oncogene expression in a series of human hepatocellular carcinomas. In an attempt to relate expression of these three oncogenes to specific stages of normal tissue differentiation, tissue sections of normal fetal, infant, and adult human livers were also examined. Of 63 cholangiocarcinomas, 59 (95%) expressed p62 c-myc, 47 (75%) expressed p21 c-ras, and 46 (73%) expressed p190 c-erbB-2. The expression of c-myc and c-ras but not of c-erb B-2 correlated directly with tumor differentiation as judged by morphologic criteria. No difference was observed in oncogene expression between intrahepatic and extrahepatic cholangiocarcinomas. Twelve of 14 hepatocellular carcinomas (86%) stained positively for all three oncoproteins. During normal liver development, expression of c-myc and c-ras was shown to occur from 18 weeks' gestation until 5 years of age, but not thereafter. Expression of c-myc, c-ras, and c-erbB-2 oncogenes may be used as immunohistochemical markers to distinguish cholangiocarcinoma from nonneoplastic biliary tissues, and may provide useful information concerning the cell biology of tumor differentiation.
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PMID:Oncogene expression in cholangiocarcinoma and in normal hepatic development. 257 40

Although signaling by the epidermal growth factor (EGF) receptor is thought to be dependent on receptor tyrosine kinase activity, it is clear that mitogen-activated protein (MAP) kinase can be activated by receptors lacking kinase activity. Since analysis of the signaling pathways used by kinase-defective receptors could reveal otherwise masked capabilities, we examined in detail the tyrosine phosphorylations and enzymes of the MAP kinase pathway induced by kinase-defective EGF receptors. Following EGF stimulation of B82L cells expressing a kinase-defective EGF receptor mutant (K721M), we found that ERK2 and ERK1 MAP kinases, as well as MEK1 and MEK2 were all activated, and SHC became prominently tyrosine-phosphorylated. By contrast, kinase-defective receptors failed to induce detectable phosphorylations of GAP (GTPase-activating protein), p62, JAK1, or p91STAT1, all of which were robustly phosphorylated by wild-type receptors. These data demonstrate that kinase-defective receptors induce several protein tyrosine phosphorylations, but that these represent only a subset of those seen with wild-type receptors. This suggests that kinase-defective receptors activate a heterologous tyrosine kinase with a specificity different from the EGF receptor. We found that kinase-defective receptors induced ErbB2/c-Neu enzymatic activation and ErbB2/c-Neu binding to SHC at a level even greater than that induced by wild-type receptors. Thus, heterodimerization with and activation of endogenous ErbB2/c-Neu is a possible mechanism by which kinase-defective receptors stimulate the MAP kinase pathway.
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PMID:An incomplete program of cellular tyrosine phosphorylations induced by kinase-defective epidermal growth factor receptors. 753 32

Heregulins (HRGs) induce tyrosine phosphorylation of several members of the erb-B family of receptors. Although originally isolated as the ligands for p185c-erb-2, recent evidence suggests that other receptors of the erbB family, including p180erbB-3 and p180erbB-4, are their true cognate receptors. Stimulation of MDA MB-453 cells with HRG beta 2 resulted in the tyrosine phosphorylation of p185c-erbB-2 and p180erbB-4 in a time- and dose-dependent fashion. This event was accompanied by the formation of multimeric complexes between the activated receptors and SH2-containing proteins. Ligand caused p120-rasGTPase activating protein (GAP), SHC and the p85 subunit of phosphatidylinositol-3'-kinase (PI3K) to be associated with both p185c-erbB-2 and p180erbB-4. In addition, tyrosine phosphorylation of p85-PI3K and SHC, but not of GAP or of its associated p62 and p190 proteins, was also detected. HRG also induced the association of GRB2 with tyrosine phosphorylated p185c-erbB-2, p180erbB-4 and SHC. Activation of mitogen-activated protein kinase (MAPK) ( > 30-fold over untreated controls) was observed upon receptor(s) activation, as it was the induction of the immediate early gene c-fos ( > 200-fold). These observations suggest that p21ras activation plays a role in the HRG pathway. Furthermore, comparative analysis of the binding of p85-PI3K to 185c-erbB-2 and p180erbB-4, revealed a preferential association with activated p180erbB-4. These findings might suggest a model of HRG action in which the relative expression of the various erb-B family members and the partitioning of signal transduction molecules between each type of receptor might determine the nature of the signal elicited by the ligand and the biological response attained.
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PMID:Signal transduction pathways induced by heregulin in MDA-MB-453 breast cancer cells. 862 88

The role of oncogenes in carcinoma of unknown primary site (CUP) has not yet been elucidated. In the present study the expression of the c-myc p62, ras p21 and c-erB-2 p185 oncoproteins were studied by a 3-step immunoperoxidase technique in 26 cases of CUP. Positive immunoreactivity was observed in 96% of the cases for c-myc, 92% for ras and in 65% for c-erb-2, with at least half of tumor cells labelled in 85%, 92% and 58% respectively. The degree of staining intensity was considered moderate or strong in more than half of the cases for all oncogene products. In conclusion, our results showed that patients with CUP have an extremely high overexpression of all three oncogenes studied. Nevertheless, the biological role of these overexpressed oncoproteins, their relationship with different histological or clinical parameters and their diagnostic or prognostic value need further evaluation.
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PMID:Overexpression of C-myc, Ras and C-erbB-2 oncoproteins in carcinoma of unknown primary origin. 866 24

An increasing number of independent studies indicate that the atypical protein kinase C (PKC) isoforms (aPKCs) are critically involved in the control of cell proliferation and survival. The aPKCs are targets of important lipid mediators such as ceramide and the products of the PI 3-kinase. In addition, the aPKCs have been shown to interact with Ras and with two novel proteins, LIP (lambda-interacting protein; a selective activator of lambda/iotaPKC) and the product of par-4 (a gene induced during apoptosis), which is an inhibitor of both lambda/iotaPKC and zetaPKC. LIP and Par-4 interact with the zinc finger domain of the aPKCs where the lipid mediators have been shown to bind. Here we report the identification of p62, a previously described phosphotyrosine-independent p56(lck) SH2-interacting protein, as a molecule that interacts potently with the V1 domain of lambda/iotaPKC and, albeit with lower affinity, with zetaPKC. We also show in this study that ectopically expressed p62 colocalizes perfectly with both lambda/iotaPKC and zetaPKC. Interestingly, the endogenous p62, like the ectopically expressed protein, displays a punctate vesicular pattern and clearly colocalizes with endogenous lambda/iotaPKC and endogenous zetaPKC. P62 colocalizes with Rab7 and partially with lamp-1 and limp-II as well as with the epidermal growth factor (EGF) receptor in activated cells, but not with Rab5 or the transferrin receptor. Of functional relevance, expression of dominant negative lambda/iotaPKC, but not of the wild-type enzyme, severely impairs the endocytic membrane transport of the EGF receptor with no effect on the transferrin receptor. These findings strongly suggest that the aPKCs are anchored by p62 in the lysosome-targeted endosomal compartment, which seems critical for the control of the growth factor receptor trafficking. This is particularly relevant in light of the role played by the aPKCs in mitogenic cell signaling events.
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PMID:Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62. 956 25


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