Mitotic lymphoma cells are characterized by high expression of phosphorylated ribosomal S6 protein

Gábor Egervári, Ágnes Márk, Melinda Hajdu, G. Barna, Z. Sápi, T. Krenács, L. Kópper, A. Sebestyén

Research output: Article

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)409-417
Number of pages9
JournalHistochemistry and Cell Biology
Volume135
Issue number4
DOIs
Publication statusPublished - ápr. 2011

Fingerprint

Ribosomal Protein S6
S 6
Lymphoma
Cell Cycle
Phosphotransferases
Lymph Nodes
Immunohistochemistry
Lymphocytes
Ribosomal Protein S6 Kinases
Nocodazole
Biopsy
Staurosporine
Sirolimus
Cell Size
Mitogens
Mitosis
Sarcoma
Paraffin
Histones
Immunosuppression

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Medical Laboratory Technology
  • Molecular Biology

Cite this

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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.",
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author = "G{\'a}bor Egerv{\'a}ri and {\'A}gnes M{\'a}rk and Melinda Hajdu and G. Barna and Z. S{\'a}pi and T. Kren{\'a}cs and L. K{\'o}pper and A. Sebesty{\'e}n",
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T1 - Mitotic lymphoma cells are characterized by high expression of phosphorylated ribosomal S6 protein

AU - Egervári, Gábor

AU - Márk, Ágnes

AU - Hajdu, Melinda

AU - Barna, G.

AU - Sápi, Z.

AU - Krenács, T.

AU - Kópper, L.

AU - Sebestyén, A.

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

KW - Cell cycle progression

KW - Lymphomas

KW - Mitosis

KW - mTOR activity

KW - S6 activity

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VL - 135

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JO - Histochemie. Histochemistry. Histochimie

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SN - 0948-6143

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