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

The protooncogene protein-tyrosine kinase c-fes plays an active role in the induction of terminal myeloid differentiation in myeloid leukemia cells. Although p93c-fes contains two autophosphorylation sites, it is not known what role they play in its catalytic or biological activities. To address this question, the major autophosphorylation site at tyrosine 713 was mutated to phenylalanine (YF713), and the mutated cDNA was expressed in a baculovirus system to assess catalytic activity, as well as in an inducible retrovirus to determine its biological activity. The major phosphopeptide in p93c-fes in vitro contained Y713 and was absent in the YF713 mutant, which exhibited an 85% loss of autophosphorylation activity. The catalytic activity of p93c-fesYF713 with either RCM-lysozyme or poly(Glu,Tyr)4:1 as substrate was reduced by 85 and 78%, respectively, in comparison to p93c-fes. Retroviral infection of K562 cells with the c-fes cDNA under the control of the mouse metallothionein promoter increased superoxide formation, phagocytosis, CD13 and CD33 antigen expression, and doubling time 4-6 days after induction. Cells infected with c-fesYF713 exhibited 40% less superoxide formation but similar levels of phagocytosis, CD13/CD33 antigen, and doubling time in comparison to cells infected with c-fes. The level of phosphotyrosine-containing proteins did not markedly differ between K562 cells expressing either neo, c-fes, or c-fesYF713, with the exception of a reduction in the level of a 210-kDa protein specifically in both c-fes-expressing cell lines. The p210 was tentatively identified as bcr-abl, whose level was also reduced in cells expressing c-fes or c-fesYF713.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the mutation of tyrosine 713 in p93c-fes on its catalytic activity and ability to promote myeloid differentiation in K562 cells. 833 28

High-grade transformation of acinic cell carcinoma (AciCC) (previously referred to as dedifferentiation) is a rare phenomenon characterized by histologic progression of low-grade AciCC to high-grade adenocarcinoma or undifferentiated carcinoma. We report 9 new cases with immunohistochemical analysis and examination of HER-2/neu and p53 genes to further define the profile of this tumor. Histologically, the high-grade component was composed of polymorphic cells with a high mitotic rate arranged in glandular and solid growth patterns with comedonecrosis. The MIB-1 labeling indices were elevated in the high-grade component, as compared with the low grade conventional AciCC. The high-grade component of AciCC was characterized by strong membrane staining for CK18 and beta-catenin, and nuclear staining for cyclin-D1. HER-2/neu, androgen receptor, C-kit, and epidermal growth factor receptor were absent from both low-grade and high-grade components. In contrast, S-100 protein, alpha-1-antitrypsin, and lysozyme were lost only in high-grade foci of transformed AciCC. The median age was 61 years (with range from 43 to 76 y). Lymph node (LN) metastases were found in 5 of 9 cases (56%). Distant metastases to the lungs (n=4), pleura (n=2), brain (n=3), and peritoneum (n=1), and paraaortic, paratracheal, and mediastinal LNs (n=2) were observed. Six of 9 patients (66%) died from tumor dissemination, all with a median overall survival of 4.3 years (range: 1 to 9 y). The high propensity for LN metastases indicates the need for neck dissection at the time of diagnosis.
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PMID:Acinic cell carcinoma with high-grade transformation: a report of 9 cases with immunohistochemical study and analysis of TP53 and HER-2/neu genes. 1946 6

The immunohistochemical features of 16 cases of papillary cystadenocarcinoma of salivary glands using a panel of monoclonal and polyclonal antibodies were evaluated. The specimens were from patients postoperatively diagnosed as papillary cystadenocarcinoma of salivary glands where the age of the patients ranged from 20-70 years, males were more commonly affected than the females and parotid gland was the most commonly affected site. The cytokeratins detected by MoAb KL1 and K8.12 were positive in all cases showing a heterogeneity in intensity of reaction. A coexpression of vimentin with cytokeratin was found in 10 cases. The tumor cells had a coexpression of S-100 protein and neuron specific enolase (NSE). Glial fibrillary acidic protein (GFAP) was positive in one case with multiple expression of cytokeratins, vimentin NSE, S-100 protein. The polymorphic mucin MAM-6 was positive in all cases and MAM-3 in 8 cases showing different intensity of reaction. The tumor cells were positive for lysozyme (8 cases), lactoferrin (10 cases) and alpha-1-antichymotrypsin (10 cases). The immunoreactive c-erbB-2 oncoprotein on the cell surface membrane was detected in 2 cases. The labeling index of proliferating cell nuclear antigen in the tumor cells ranged from 3.8 to 43.2% (mean 14.2 +/- standard deviation 9.8). Histopathological feature and a heterogeneity of multiple expression of tissue markers may suggest that a population of cells in papillary cystadenocarcinoma may be counterparts of modified myoepithelial cells of pleomorphic adenoma that express epithelial, mesenchymal and neuronal differentiation although the role of myoepithelial cells in the genesis of this tumor is not clear. However, disorganized stratification and malignant transformation of ductal cells may be the most likely possibility in the histogenesis of this tumor.
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PMID:Papillary cystadenocarcinoma of salivary-glands - an immunohistochemical study. 2156 64