title: Cortactin, another player in the Lyn signaling pathway, is over-expressed and alternatively spliced in leukemic cells from patients with B-cell chronic lymphocytic leukemia.
abstract: Cortactin, an actin binding protein and Lyn substrate, is up-regulated in several cancers and its level is associated with increased cell migration, metastasis and poor prognosis. The identification that the Src kinase Lyn and its substrate HS1 are over-expressed in B-cell chronic lymphocytic leukemia and involved in resistance to chemotherapy and poor prognosis, prompted us to investigate the role of cortactin, an HS1 homolog, in the pathogenesis and progression of this disorder. In this study, we observed that cortactin is over-expressed in leukemic cells of patients (1.10 ± 0.12) with respect to normal B lymphocytes (0.19 ± 0.06; P=0.0065). Fifty-three percent of our patients expressed the WT mRNA and p80/85 protein isoforms, usually lacking in normal B lymphocytes which express the SV1 variant and the p70/75 protein isoforms. Moreover, we found an association of the cortactin overexpression and negative prognostic factors, including ZAP-70 (P<0.01), CD38 (P<0.01) and somatic hypermutations in the immunoglobulin heavy-chain variable region (P<0.01). Our results show that patients with B-cell chronic lymphocytic leukemia express high levels of cortactin with a particular overexpression of the WT isoform that is lacking in normal B cells, and a correlation to poor prognosis, suggesting that this protein could be relevant in the pathogenesis and aggressiveness of the disease.
authors: Departement of Medicine, Hematology and Clinical Immunology Branch, Padova University School of Medicine, Italy Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Cristina
authors: C
authors: Gattazzo
authors: Departement of Medicine, Hematology and Clinical Immunology Branch, Padova University School of Medicine, Italy Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Veronica
authors: V
authors: Martini
authors: Departement of Medicine, Hematology and Clinical Immunology Branch, Padova University School of Medicine, Italy Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Federica
authors: F
authors: Frezzato
authors: Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Valentina
authors: V
authors: Trimarco
authors: Department of Molecular Medicine, University of Padova, Italy.
authors: Elena
authors: E
authors: Tibaldi
authors: Departement of Medicine, Hematology and Clinical Immunology Branch, Padova University School of Medicine, Italy.
authors: Monica
authors: M
authors: Castelli
authors: Departement of Medicine, Hematology and Clinical Immunology Branch, Padova University School of Medicine, Italy Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Monica
authors: M
authors: Facco
authors: Department of Molecular Medicine, University of Padova, Italy.
authors: Francesca
authors: F
authors: Zonta
authors: Department of Molecular Medicine, University of Padova, Italy.
authors: Anna Maria
authors: AM
authors: Brunati
authors: Departement of Medicine, Hematology and Clinical Immunology Branch, Padova University School of Medicine, Italy Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Renato
authors: R
authors: Zambello
authors: Departement of Medicine, Hematology and Clinical Immunology Branch, Padova University School of Medicine, Italy Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Gianpietro
authors: G
authors: Semenzato
authors: Departement of Medicine, Hematology and Clinical Immunology Branch, Padova University School of Medicine, Italy Venetian Institute of Molecular Medicine, Padova, Italy livio.trentin@unipd.it.
authors: Livio
authors: L
authors: Trentin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D051356:Cortactin / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D051356:Cortactin; D020033:Protein Isoforms; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases