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PMID: 17179226 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA.

Blood ·Vol. 109 ·No. 7 ·2007-04-01 ·Pages 3069-75

Otake Y, Soundararajan S, Sengupta TK, Kio EA, Smith JC, Pineda-Roman M, Stuart RK, Spicer EK, Fernandes DJ

Abstract

B-cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells that are resistant to apoptosis as a result of bcl2 oncogene overexpression. Studies were done to determine the mechanism for the up-regulation of bcl-2 protein observed in CD19+ CLL cells compared with CD19+ B cells from healthy volunteers. The 11-fold higher level of bcl-2 protein in CLL cells was positively correlated with a 26-fold elevation in the cytosolic level of nucleolin, a bcl2 mRNA-stabilizing protein. Measurements of the bcl2 heterogeneous nuclear/bcl2 mRNA (hnRNA)/mRNA ratios and the rates of bcl2 mRNA decay in cell extracts indicated that the 3-fold higher steady-state level of bcl2 mRNA in CLL cells was the result of increased bcl2 mRNA stability. Nucleolin was present throughout the nucleus and cytoplasm of CLL cells, whereas in normal B cells nucleolin was only detected in the nucleus. The addition of recombinant human nucleolin to extracts of normal B cells markedly slowed the rate of bcl2 mRNA decay. SiRNA knockdown of nucleolin in MCF-7 cells resulted in decreased levels of bcl2mRNA and protein but no change in beta-actin. These results indicate that bcl-2 overexpression in CLL cells is related to stabilization of bcl2 mRNA by nucleolin.

MeSH Terms
B-Lymphocytes/drug effects,metabolism Cell Line, Tumor Cell Nucleus/metabolism Cytoplasm/metabolism Female Gene Expression Genes, bcl-2 Humans In Vitro Techniques Leukemia, Lymphocytic, Chronic, B-Cell/genetics,metabolism Male Phosphoproteins/antagonists & inhibitors,genetics,metabolism,pharmacology RNA Stability RNA, Messenger/genetics,metabolism RNA, Small Interfering/genetics RNA-Binding Proteins/antagonists & inhibitors,genetics,metabolism,pharmacology Recombinant Proteins/genetics,pharmacology
Chemicals
Phosphoproteins RNA, Messenger RNA, Small Interfering RNA-Binding Proteins Recombinant Proteins nucleolin
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Otake Yoko
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Soundararajan Sridharan
Sengupta Tapas K
Kio Ebenezer A
Smith James C
Pineda-Roman Mauricio
Stuart Robert K
Spicer Eleanor K
Fernandes Daniel J
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-08-043257
Published
2007-04-01
Pages
3069-75
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1852223
Subset
IM
Grants
NCI NIH HHS · R01 CA083925 · United States
NCI NIH HHS · R01 CA109254 · United States
NCI NIH HHS · CA109254 · United States
NCI NIH HHS · CA83925 · United States
External Links
PubMed source DOI: 10.1182/blood-2006-08-043257 PMC Full Text View journal details
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