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Cellular, Molecular, and Tumor Biology 33: Inflammation and Metastasis

Human immunodeficiency virus-1 Tat protein upregulates IL-6 and IL-8 expression in human breast cancer cells

Yongwoo Lee, Natasha Kyprianou, Avindra Nath and Michal Toborek
Yongwoo Lee
University of Kentucky, Lexington, KY and Johns Hopkins University, Baltimore, MD
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Natasha Kyprianou
University of Kentucky, Lexington, KY and Johns Hopkins University, Baltimore, MD
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Avindra Nath
University of Kentucky, Lexington, KY and Johns Hopkins University, Baltimore, MD
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Michal Toborek
University of Kentucky, Lexington, KY and Johns Hopkins University, Baltimore, MD
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DOI:  Published April 2004
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Proc Amer Assoc Cancer Res, Volume 45, 2004

Abstract

1752

It has been proposed that the inflammatory tumor microenvironment via overexpression of inflammatory mediators is associated with progression of breast cancer metastasis in human immunodeficiency virus (HIV)-infected women. The cellular and molecular regulatory mechanisms underlying this process, however, are not fully understood. In the present study, we hypothesize that HIV-1 Tat protein may increase the metastatic potential of human breast cancer cells through upregulation of cytokines and chemokines that induce the inflammatory tumor microenvironment. Real-time reverse transcriptase-polymerase chain reaction and the quantitative sandwich enzyme immunoassay analyses showed that exposure of MDA-MB-231 cells to HIV-1 Tat protein resulted in a significant and dose-dependent upregulation of interleukin-6 (IL-6) and interleukin-8 (IL-8) mRNA and protein expression. HIV-1 Tat protein also markedly increased NF-κB DNA-binding activity and transactivation in MDA-MB-231 cells. Additionally, pretreatment with NF-κB inhibitors significantly attenuated the ability of HIV-1 Tat protein to upregulate IL-6 and IL-8 expression. These results suggest that HIV-1 Tat protein upregulates expression of IL-6 and IL-8 in human breast cancer cells by NF-κB-dependent pathway. These data may contribute to exploration of the new molecular mechanisms leading to novel approaches for the therapeutic drug developments specifically targeted against the inflammatory pathways of breast cancer metastasis in AIDS patients (This work was supported by NIH COBRE P20 RR 15592, NS39254, MH63022, and AA013843).

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April 2004
Volume 64, Issue 7 Supplement
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Human immunodeficiency virus-1 Tat protein upregulates IL-6 and IL-8 expression in human breast cancer cells
Yongwoo Lee, Natasha Kyprianou, Avindra Nath and Michal Toborek
Cancer Res April 1 2004 (64) (7 Supplement) 403;

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Human immunodeficiency virus-1 Tat protein upregulates IL-6 and IL-8 expression in human breast cancer cells
Yongwoo Lee, Natasha Kyprianou, Avindra Nath and Michal Toborek
Cancer Res April 1 2004 (64) (7 Supplement) 403;
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