Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microfilaments are associated with the microvillar membrane in the 13762 ascites rat mammary carcinoma cells by stable interaction with a large, multimeric signal transduction particle (STP) containing the (proto)oncogene receptor p185(neu). In vitro kinase assays on isolated microvilli and microvillar fractions enriched in the putative signal transduction particle showed a high specific activity of tyrosine kinase activity compared to that of membranes from EGF receptor-overexpressing A431 cells maximally activated by EGF. Assays of velocity sedimentation fractions from microvillar lysates in the presence and absence of the exogenous tyrosine kinase substrate poly-glu-tyr polypeptide (poly-E(4)Y) suggested association of the tyrosine kinase activity with STP-enriched microvillar fractions. The particulate fractions also contained discrete endogenous tyrosine-phosphorylated proteins, including prominent bands of approximately 42 and 58 kDa. Addition of ATP to these fractions resulted in a rapid increase in tyrosine phosphorylation of these and several other proteins, as detected by anti-phosphotyrosine blots. Immunoprecipitation and immunoblotting with anti-phosphotyrosine antibody of SDS-solubilized ascites cells and microfilament core fractions showed nine major bands; the electrophoretic mobilities of most of these in the cell immunoprecipitate and microfilament core were the same. In vivo and in situ phosphorylation, phosphoamino acid analysis, immunoprecipitation, 2-dimensional isoelectric focusing/SDS PAGE and immunoblot analysis showed that one of the prominent substrates is p58(gag), a retroviral Gag-like cytoplasmic STP component implicated in stabilizing microfilament-membrane interactions. Immunoblotting identified two peripheral membrane tyrosine kinases, p6O(src) and p120(abl), stably associated with the p185(neu)-containing signal transduction particle. These results provide further evidence for the constitutive activation of this aggressive mammary tumor and suggest a rote for phosphorylation of p58(gag) in organization of the STP at the membrane-microfilament interface in these cells.
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PMID:Tyrosine phosphorylation at the membrane-microfilament interface: a p185neu-associated signal transduction particle containing Src, Abl and phosphorylated p58, a membrane- and microfilament-associated retroviral gag-like protein. 864 94

Tubulolobular carcinoma is a type of mammary carcinoma that displays an admixture of invasive tubules and lobular-like cells. Previous reports have shown it to share clinical similarities to lobular carcinoma, whereas more recent studies have shown it to be E-cadherin positive. The aim of the current study was to further explore the immunophenotype of tubulolobular carcinoma, and to document its natural behavior. Nineteen cases of tubulolobular carcinoma and 10 cases each of tubular and lobular carcinoma were retrieved for comparison analysis. Immunohistochemistry was performed with antibodies against estrogen receptor, progesterone receptor, HER2/neu, 34betaE12, E-cadherin, and the catenins. Twenty-five percent of patients with tubulolobular carcinoma presented with greater than stage I disease, compared to 0 and 60% of patients with tubular and lobular carcinoma, respectively. Two patients with tubulolobular carcinoma had tumor recurrence, one of whom also developed metastasis. The majority of all carcinomas were estrogen and progesterone receptor positive. E-cadherin displayed membranous staining in all tubular and tubulolobular carcinomas, and was negative in all lobular carcinomas. Half of each carcinoma subtype displayed granular cytoplasmic 34betaE12 immunoreactivity. alpha-Catenin exhibited partial or complete membranous staining in all tubulolobular and tubular carcinomas, and was negative in all lobular carcinomas. beta-Catenin displayed membranous staining in tubulolobular and tubular carcinomas, whereas all lobular carcinomas had coarse cytoplasmic immunoreactivity. p120 and gamma-catenin displayed membranous staining in 100% of tubulolobular and tubular carcinomas and cytoplasmic staining in 100% of lobular carcinomas. Tubulolobular carcinoma of the breast is thus a distinct type of mammary carcinoma that displays both tubular and lobular patterns histologically but displays the membranous E-cadherin/catenin complex characteristic of the ductal immunophenotype. Tubulolobular carcinoma appears to be more aggressive than tubular carcinoma, as 16% of patients had lymph node metastases, although all were alive at a mean follow-up of 40 months.
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PMID:The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast: an immunohistochemical and clinicopathologic study. 1865 93

Invasive lobular carcinomas (ILC) of breast typically demonstrate intracytoplasmic mucin. We present a unique case of classical type ILC with abundant extracellular mucin and strong ERBB2 (HER2/neu) expression confirmed by immunohistochemistry and fluorescent in situ hybridization. Dual E-cadherin/p120 immunohistochemical stain demonstrated complete loss of membranous E-cadherin and the presence of diffuse cytoplasmic p120 staining, confirming the lobular phenotype. The tumor cells showed ductal-like cytoplasmic MUC1 staining, but were negative for MUC2 and other mucin gene markers. In addition, studies of tissue microarrays of 80 breast carcinomas with mucinous differentiation revealed 4 pure mucinous carcinomas showing significantly reduced E-cadherin staining without redistribution of p120 into cytoplasm. The findings suggest that the presence of extracellular mucin does not exclude a diagnosis of lobular carcinoma, and the morphologic and molecular characteristics of lobular and ductal carcinomas are more complex than previously appreciated.
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PMID:Invasive lobular carcinoma with extracellular mucin production and HER-2 overexpression: a case report and further case studies. 2055 Jun 96