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Title: DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma

Abstract

DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines, Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy.

Authors:
 [1];  [2]; ; ;  [1]; ; ; ;  [3];  [1]
  1. Laboratory of Cancer Research, Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kitaku, Sapporo 060-8638 (Japan)
  2. Laboratory of Translational Pathology, Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kitaku, Sapporo 060-8638 (Japan)
  3. Department of Medicine II, Hokkaido University Graduate School of Medicine, N15W7, Kitaku, Sapporo 060-8638 (Japan)
Publication Date:
OSTI Identifier:
22202494
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 395; Journal Issue: 1; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CELL PROLIFERATION; LYMPHOMAS; MICE; PROTEINS; TUMOR CELLS

Citation Formats

Wang, Lei, Nishihara, Hiroshi, E-mail: nisihara@patho2.med.hokudai.ac.jp, Kimura, Taichi, Kato, Yasutaka, Tanino, Mishie, Nishio, Mitsufumi, Obara, Masato, Endo, Tomoyuki, Koike, Takao, and Tanaka, Shinya. DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.03.148.
Wang, Lei, Nishihara, Hiroshi, E-mail: nisihara@patho2.med.hokudai.ac.jp, Kimura, Taichi, Kato, Yasutaka, Tanino, Mishie, Nishio, Mitsufumi, Obara, Masato, Endo, Tomoyuki, Koike, Takao, & Tanaka, Shinya. DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma. United States. doi:10.1016/J.BBRC.2010.03.148.
Wang, Lei, Nishihara, Hiroshi, E-mail: nisihara@patho2.med.hokudai.ac.jp, Kimura, Taichi, Kato, Yasutaka, Tanino, Mishie, Nishio, Mitsufumi, Obara, Masato, Endo, Tomoyuki, Koike, Takao, and Tanaka, Shinya. 2010. "DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma". United States. doi:10.1016/J.BBRC.2010.03.148.
@article{osti_22202494,
title = {DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma},
author = {Wang, Lei and Nishihara, Hiroshi, E-mail: nisihara@patho2.med.hokudai.ac.jp and Kimura, Taichi and Kato, Yasutaka and Tanino, Mishie and Nishio, Mitsufumi and Obara, Masato and Endo, Tomoyuki and Koike, Takao and Tanaka, Shinya},
abstractNote = {DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines, Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy.},
doi = {10.1016/J.BBRC.2010.03.148},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 395,
place = {United States},
year = 2010,
month = 4
}
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