Document Detail


Up-regulation of proliferative and migratory genes in regulatory T cells from patients with metastatic castration-resistant prostate cancer.
MedLine Citation:
PMID:  23319273     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A higher frequency of regulatory T cells (Tregs) has been observed in peripheral blood mononuclear cells (PBMC) of patients with different types of solid tumors and hematological malignancies as compared to healthy donors. In prostate cancer patients, Tregs in PBMC have been shown to have increased suppressive function. Tumor-induced biological changes in Tregs may enable tumor cells to escape immunosurveillance. We performed genome-wide expression analyses comparing the expression levels of more than 38,500 genes in Tregs with similar suppressive activity, isolated from the peripheral blood of healthy donors and patients with metastatic castration-resistant prostate cancer (mCRPC). The differentially expressed genes in mCRPC Tregs are involved in cell cycle processes, cellular growth and proliferation, immune responses, hematological system development and function and the interleukin-2 (IL-2) and transforming growth factor-β (TGF-β) pathways. Studies revealed that the levels of expression of genes responsible for T-cell proliferation (C-FOS, C-JUN and DUSP1) and cellular migration (RGS1) were greater in Tregs from mCRPC patients as compared to values observed in healthy donors. Increased RGS1 expression in Tregs from mCRPC patients suggests a decrease in these Tregs' migratory ability. In addition, the higher frequency of CD4(+) CD25(high) CD127(-) Tregs in the peripheral blood of mCRPC patients may be the result of an increase in Treg proliferation capacity. Results also suggest that the alterations observed in gene expression profiles of Tregs in mCRPC patients may be part of the mechanism of tumor escape from host immune surveillance.
Authors:
Ngar-Yee Huen; Alan Lap-Yin Pang; Jo A Tucker; Tin-Lap Lee; Matteo Vergati; Caroline Jochems; Chiara Intrivici; Vittore Cereda; Wai-Yee Chan; Owen M Rennert; Ravi A Madan; James L Gulley; Jeffrey Schlom; Kwong Y Tsang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2013-02-12
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-05-15     Completed Date:  2013-07-11     Revised Date:  2014-08-05    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  373-82     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Cell Movement
Cell Proliferation
Clinical Trials, Phase II as Topic
Dual Specificity Phosphatase 1 / metabolism
Gene Expression Regulation, Neoplastic*
Humans
Interleukin-2 / metabolism
Leukocytes, Mononuclear / cytology
Male
Middle Aged
Multicenter Studies as Topic
Neoplasm Metastasis
Prostatic Neoplasms / immunology,  metabolism,  pathology*
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
RGS Proteins / metabolism
Randomized Controlled Trials as Topic
T-Lymphocytes, Regulatory / cytology*
Transforming Growth Factor beta / metabolism
Up-Regulation*
Young Adult
Grant Support
ID/Acronym/Agency:
Z01 BC010973-01/BC/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-2; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RGS Proteins; 0/RGS1 protein, human; 0/Transforming Growth Factor beta; EC 3.1.3.48/DUSP1 protein, human; EC 3.1.3.48/Dual Specificity Phosphatase 1
Comments/Corrections

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