The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells.

The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Research Abstract Details 

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The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Abstract Text:

Simona Colla,Fenghuang Zhan,Wei Xiong,Xiaosong Wu,Hongwei Xu,Owen Stephens,Shmuel Yaccoby,Joshua Epstein,Bart Barlogie,John D Shaughnessy,

Multiple myeloma (MM) plasma cells, but not those from healthy donors and patients with monoclonal gammopathy of undetermined significance or other plasma cell dyscrasias involving the bone marrow, express the Wnt-signaling antagonist DKK1. We previously reported that secretion of DKK1 by MM cells likely contributes to osteolytic lesions in this disease by inhibiting Wnt signaling, which is essential for osteoblast differentiation and survival. The mechanisms responsible for activation and regulation of DKK1 expression in MM are not known. Herein, we could trace DKK1 expression changes in MM cells to perturbations in the JNK signaling cascade, which is differentially modulated through oxidative stress and interactions between MM cells with osteoclasts in vitro. Despite its role as a tumor suppressor and mediator of apoptosis in other cell types including osteoblasts, our data suggest that DKK1, a stress-responsive gene in MM, does not mediate apoptotic signaling, is not activated by TP53, and its forced overexpression could not inhibit cell growth or sensitize MM cells to apoptosis following treatment with thalidomide or lenalidomide. We conclude that specific strategies to modulate persistent activation of the JNK pathway may be beneficial in preventing disease progression and treating myeloma-associated bone disease by inhibiting DKK1 expression.

The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Publishing Authors By Initials

S Colla,F Zhan,W Xiong,X Wu,H Xu,O Stephens,S Yaccoby,J Epstein,B Barlogie,JD Shaughnessy,

For similar proteins: dna-binding proteins: tumor suppressor protein p53 research abstracts see: proteins: dna-binding proteins: tumor suppressor protein p53 research

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The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Blood

VOLUME: 109

Page Numbers: 4470-7

Journal Abbreviation:

ISSN: 0006-4971

DAY: 25

MONTH: 01

YEAR: 2007

The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7603509

The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Protein p53

MESH TERMS: physiology

Chemical & Substance for Abstract: The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Information

Substance Name: JNK Mitogen-Activated Protein Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells.

AFFILIATION: Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA97513

ACRONYM: CA

MEDLINETA: Blood

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