title: Mitotic lymphoma cells are characterized by high expression of phosphorylated ribosomal S6 protein.
abstract: Growth factors and mitogens influence signaling pathways and often induce the activity of p70S6 kinase (p70S6K), which in turn phosphorylates the ribosomal S6 protein (S6). Although recent data are rather conflicting, the overall view suggests that phosphorylated S6 is a regulator of global protein synthesis, cell proliferation, cell size and glucose homeostasis. In the present work, emphasis was given to cell cycle-dependent activation of S6 focusing mainly on human lymphoid and lymphoma cells. Paraffin-embedded human tissue blocks from lymph node and different tumor biopsies as well as in vitro cell lines were investigated by immunohistochemistry, immunocytochemistry, flow cytometry and Western blotting using antibodies directed against phospho-S6, phospho-mTOR, phospho-p70S6K and phospho-Histone H3. To enrich the cell number in different phases of the cell cycle, nocodazole, staurosporine or rapamycin were used in cell cultures. We observed strong phospho-S6 positivity by immunostainings in the dividing lymphoid cells of reactive lymph nodes and in lymphoma cells cultured in vitro. Phospho-S6 protein levels were shown to be elevated throughout mitosis in lymphoma cells; however, the high expression of phospho-S6 in mitotic cells was not a general hallmark of tumor cell types studied so far: phospho-S6-negative mitotic cells were detected in several carcinoma and sarcoma biopsies. These observations may have practical implications as they raise the possibility to consider p70S6K and/or S6 as a potential therapeutic target-besides mTOR-in certain lymphomas and perhaps in clinical immunosuppression.
authors.affiliation: 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Üllői út 26, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Egervári
authors.forename: Agnes
authors.initials: A
authors.lastname: Márk
authors.forename: Melinda
authors.initials: M
authors.lastname: Hajdu
authors.forename: Gábor
authors.initials: G
authors.lastname: Barna
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Sápi
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenács
authors.forename: László
authors.initials: L
authors.lastname: Kopper
authors.forename: Anna
authors.initials: A
authors.lastname: Sebestyén
mesh_terms: D015153:Blotting, Western; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology*; D008938:Mitosis; D010766:Phosphorylation; D038601:Ribosomal Protein S6 / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D038601:Ribosomal Protein S6