Human immunodeficiency virus-1 Tat protein up-regulates interleukin-6 and interleukin-8 expression in human breast cancer cells

Y. W. Lee, A. A. Hirani, N. Kyprianou, Michal J Toborek

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objective: To examine whether HIV-1 Tat protein increases the metastatic potential of human breast cancer cells through induction of pro-inflammatory tumor microenvironment. Methods: Real-time RT-PCR and ELISA were employed to determine the mRNA and protein expression of IL-6 and IL-8 in highly metastatic human breast cancer cell line, MDA-MB-231. To investigate the transcriptional regulatory mechanisms of Tat-mediated up-regulation of IL-6 and IL-8, EMSA and reporter gene assay were carried out. Results: Exposure of MDA-MB-231 cells to Tat resulted in a significant and dose-dependent up-regulation of IL-6 and IL-8 mRNA and protein expression. HIV-1 Tat protein also markedly increased NF-κB DNA-binding activity and trans-activation in MDA-MB-231 cells. Additionally, pretreatment with NF-κB inhibitors significantly attenuated the ability of Tat to up-regulate IL-6 and IL-8 expression. It was also found that exposure of MDA-MB-231 cells to Tat induced up-regulation of MMP-9 expression at both mRNA and protein levels. Conclusions: These results suggest that HIV-1 Tat protein up-regulates 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.

Original languageEnglish
Pages (from-to)380-389
Number of pages10
JournalInflammation Research
Volume54
Issue number9
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Fingerprint

tat Gene Products
Interleukin-8
Viruses
Human Immunodeficiency Virus tat Gene Products
HIV-1
Interleukin-6
Up-Regulation
Cells
Breast Neoplasms
Messenger RNA
Inflammatory Breast Neoplasms
Proteins
Tumor Microenvironment
Matrix Metalloproteinases
Reporter Genes
Tumors
Real-Time Polymerase Chain Reaction
Assays
Acquired Immunodeficiency Syndrome
Genes

Keywords

  • AIDS
  • Inflammation
  • MDA-MB-231
  • Metastasis
  • NF-κB

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology (medical)
  • Immunology
  • Cell Biology

Cite this

Human immunodeficiency virus-1 Tat protein up-regulates interleukin-6 and interleukin-8 expression in human breast cancer cells. / Lee, Y. W.; Hirani, A. A.; Kyprianou, N.; Toborek, Michal J.

In: Inflammation Research, Vol. 54, No. 9, 01.09.2005, p. 380-389.

Research output: Contribution to journalArticle

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abstract = "Objective: To examine whether HIV-1 Tat protein increases the metastatic potential of human breast cancer cells through induction of pro-inflammatory tumor microenvironment. Methods: Real-time RT-PCR and ELISA were employed to determine the mRNA and protein expression of IL-6 and IL-8 in highly metastatic human breast cancer cell line, MDA-MB-231. To investigate the transcriptional regulatory mechanisms of Tat-mediated up-regulation of IL-6 and IL-8, EMSA and reporter gene assay were carried out. Results: Exposure of MDA-MB-231 cells to Tat resulted in a significant and dose-dependent up-regulation of IL-6 and IL-8 mRNA and protein expression. HIV-1 Tat protein also markedly increased NF-κB DNA-binding activity and trans-activation in MDA-MB-231 cells. Additionally, pretreatment with NF-κB inhibitors significantly attenuated the ability of Tat to up-regulate IL-6 and IL-8 expression. It was also found that exposure of MDA-MB-231 cells to Tat induced up-regulation of MMP-9 expression at both mRNA and protein levels. Conclusions: These results suggest that HIV-1 Tat protein up-regulates 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.",
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