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Similarities of prosurvival signals in Bcl-2-positive and Bcl-2-negative follicular lymphomas identified by reverse phase protein microarray. 2004

Hongbin Zha, and Mark Raffeld, and Lu Charboneau, and Stefania Pittaluga, and Larry W Kwak, and Emanuel Petricoin, and Lance A Liotta, and Elaine S Jaffe
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Overexpression of Bcl-2 protein has been known to play a role in the pathogenesis of follicular lymphoma (FL). However, 10-15% of FLs are negative for Bcl-2 by immunohistochemistry, raising the possibility that another gene product(s) may provide prosurvival signal(s). We used reverse phase protein microarray to analyze lysates of follicle center cells isolated by laser capture microdissection from: Bcl-2+ FL, Bcl-2- FL and reactive follicular hyperplasia (FH) (nine cases each group). TUNEL assay confirmed similar and reduced levels of apoptosis in Bcl-2+ FL and Bcl-2- FL, indicating the likelihood of Bcl-2-independent inhibition of apoptosis. Arrays were quantitatively analyzed with antibodies to proteins involved in the apoptotic pathway. As expected, Bcl-2 levels were up to eight-fold higher in Bcl-2+ FL than in FH and Bcl-2- FL. However, there was no difference in levels of Mcl-1 and survivin among these three groups. Bcl-X(L) showed a trend for increased expression in Bcl-2- FL as compared with Bcl-2+ FL, although the differences did not reach statistical significance (P>0.1). The increase in Bcl-X(L) may provide an alternative antiapoptotic signal in FL negative for Bcl-2 protein. Interestingly, Bax expression was higher in FL (Bcl-2+ or -) than in FH (P=0.001). Notably, phospho-Akt (Ser-473) was increased in FL (Bcl-2+ or -) (P<0.03) with increased phospho-Bad (Ser-136), as compared with levels in FH. The activation of the Akt/Bad pathway provides further evidence of prosurvival signals in FL, independent of Bcl-2 alone. These data suggest that nodal FL represents a single disease with a final common biochemical pathway.

UI MeSH Term Description Entries
D007091 Image Processing, Computer-Assisted A technique of inputting two-dimensional or three-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer. Biomedical Image Processing,Computer-Assisted Image Processing,Digital Image Processing,Image Analysis, Computer-Assisted,Image Reconstruction,Medical Image Processing,Analysis, Computer-Assisted Image,Computer-Assisted Image Analysis,Computer Assisted Image Analysis,Computer Assisted Image Processing,Computer-Assisted Image Analyses,Image Analyses, Computer-Assisted,Image Analysis, Computer Assisted,Image Processing, Biomedical,Image Processing, Computer Assisted,Image Processing, Digital,Image Processing, Medical,Image Processings, Medical,Image Reconstructions,Medical Image Processings,Processing, Biomedical Image,Processing, Digital Image,Processing, Medical Image,Processings, Digital Image,Processings, Medical Image,Reconstruction, Image,Reconstructions, Image
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008198 Lymph Nodes They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system. Lymph Node,Node, Lymph,Nodes, Lymph
D008224 Lymphoma, Follicular Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES. Brill-Symmers Disease,Follicular Lymphoma,Lymphoma, Giant Follicular,Lymphoma, Nodular,Follicular Large-Cell Lymphoma,Follicular Lymphoma, Giant,Follicular Lymphoma, Grade 1,Follicular Lymphoma, Grade 2,Follicular Lymphoma, Grade 3,Follicular Mixed-Cell Lymphoma,Giant Follicular Lymphoma,Histiocytic Lymphoma, Nodular,Large Lymphoid Lymphoma, Nodular,Large-Cell Lymphoma, Follicular,Lymphocytic Lymphoma, Nodular, Poorly Differentiated,Lymphocytic Lymphoma, Nodular, Poorly-Differentiated,Lymphoma, Follicular Large-Cell,Lymphoma, Follicular, Grade 1,Lymphoma, Follicular, Grade 2,Lymphoma, Follicular, Grade 3,Lymphoma, Follicular, Mixed Cell,Lymphoma, Follicular, Mixed Lymphocytic-Histiocytic,Lymphoma, Follicular, Mixed Small and Large Lymphoid,Lymphoma, Follicular, Small and Large Cleaved Cell,Lymphoma, Follicular, Small and Large Cleaved-Cell,Lymphoma, Histiocytic, Nodular,Lymphoma, Large Cell, Follicular,Lymphoma, Large Lymphoid, Nodular,Lymphoma, Large-Cell, Follicular,Lymphoma, Lymphocytic, Nodular, Poorly Differentiated,Lymphoma, Lymphocytic, Nodular, Poorly-Differentiated,Lymphoma, Mixed-Cell, Follicular,Lymphoma, Nodular, Large Follicular Center Cell,Lymphoma, Nodular, Large Follicular Center-Cell,Lymphoma, Nodular, Mixed Lymphocytic Histiocytic,Lymphoma, Nodular, Mixed Lymphocytic-Histiocytic,Lymphoma, Nodular, Mixed Small and Large Cell,Lymphoma, Small Cleaved Cell, Follicular,Lymphoma, Small Cleaved-Cell, Follicular,Lymphoma, Small Follicular Center-Cell,Lymphoma, Small Lymphoid, Follicular,Mixed-Cell Lymphoma, Follicular,Nodular Large Follicular Center-Cell Lymphoma,Small Cleaved-Cell Lymphoma, Follicular,Small Follicular Center-Cell Lymphoma,Brill Symmers Disease,Disease, Brill-Symmers,Follicular Large Cell Lymphoma,Follicular Large-Cell Lymphomas,Follicular Lymphomas,Follicular Lymphomas, Giant,Follicular Mixed Cell Lymphoma,Follicular Mixed-Cell Lymphomas,Giant Follicular Lymphomas,Histiocytic Lymphomas, Nodular,Large Cell Lymphoma, Follicular,Large-Cell Lymphomas, Follicular,Lymphoma, Follicular Large Cell,Lymphoma, Follicular Mixed-Cell,Lymphoma, Nodular Histiocytic,Lymphoma, Small Follicular Center Cell,Lymphomas, Follicular,Lymphomas, Follicular Large-Cell,Lymphomas, Follicular Mixed-Cell,Lymphomas, Giant Follicular,Lymphomas, Nodular,Lymphomas, Nodular Histiocytic,Mixed Cell Lymphoma, Follicular,Mixed-Cell Lymphomas, Follicular,Nodular Histiocytic Lymphoma,Nodular Histiocytic Lymphomas,Nodular Large Follicular Center Cell Lymphoma,Nodular Lymphoma,Nodular Lymphomas,Small Cleaved Cell Lymphoma, Follicular,Small Follicular Center Cell Lymphoma
D008869 Microtubule-Associated Proteins High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules. Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D009367 Neoplasm Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier

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