Format

Send to

Choose Destination
Hum Pathol. 2014 Mar;45(3):565-72. doi: 10.1016/j.humpath.2013.10.024. Epub 2013 Oct 31.

c-JUN N-terminal kinase (JNK) is activated and contributes to tumor cell proliferation in classical Hodgkin lymphoma.

Author information

1
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; First Department of Pathology, National and Kapodistrian University of Athens, Athens 11527, Greece.
2
Department of Pathology, Medical School, University of Crete, Heraklion Crete 71003, Greece.
3
First Department of Pathology, National and Kapodistrian University of Athens, Athens 11527, Greece.
4
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
5
Laboratory of Cancer Biology, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas (FORTH), 70013 Heraklion, Greece.
6
Department of Hematology, National and Kapodistrian University of Athens, Athens 11527, Greece.
7
Department of Hematology, Medical School, University of Crete, Heraklion Crete 71003, Greece.
8
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; First Department of Pathology, National and Kapodistrian University of Athens, Athens 11527, Greece. Electronic address: grassidakis@hotmail.com.

Abstract

c-JUN N-terminal Kinase (JNK) is activated/phosphorylated by upstream MAPK kinases (MKK), and, in turn, phosphorylates and activates its major substrate c-JUN, a member of the activator protein-1 (AP-1) transcription factors. c-JUN is overexpressed and activated in Hodgkin and Reed Sternberg cells (HRS) of classical Hodgkin lymphoma (cHL), however, the mechanism of its activation remains unknown. JNK activation was immunohistochemically assessed in 60 cases of HL and in a control group of 151 B-cell non-Hodgkin lymphomas. The biologic effects of JNK activation in cultured HRS cells were investigated using colony formation, cell growth and viability assays and cell cycle analysis by flow cytometry. Western blotting was used to assess protein levels. p-JNK was expressed in 90% of HL, 83% of Burkitt lymphomas, 28% of mantle cell lymphomas, 23% of diffuse large B-cell lymphomas, 19% of follicular lymphomas, and 18% of extranodal marginal zone lymphomas of MALT type. None of the 48 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma and 18 cases of plasma cell myeloma showed JNK phosphorylation (P < 001, Kruskall-Wallis test). Pharmacological inhibition of JNK activity in cultured HRS cells resulted in a significant decrease of cell growth, which was associated with cell cycle arrest at the G2/M phase. The cell cycle effects were linked to deactivation of c-JUN and upregulation of its known target, the cyclin-dependent kinase inhibitor p21. JNK is highly activated in HRS cells, and may contribute to uncontrolled cell cycle progression and proliferation of tumor cells in cHL.

KEYWORDS:

Cell cycle; Hodgkin lymphoma; JNK; Non-Hodgkin lymphoma; c-JUN; p21

PMID:
24457077
DOI:
10.1016/j.humpath.2013.10.024
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center