Expression of an antisense transforming growth factor-β1 transgene reduces tumorigenicity of EMT6 mammary tumor cells

Julie A. Park, Ena Wang, Robert A. Kurt, Samuel F. Schluter, Evan M. Hersh, Emmanuel T. Akporiaye

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) is a potent immunosuppressive cytokine produced by many tumor cells. Secretion of TGF-β by malignant cells may therefore be a mechanism by which tumor cells escape destruction by tumor-specific T lymphocytes. In order to evaluate the role of tumor-derived TGF-β on tumor progression, we have inhibited the production of this cytokine by introducing a gene encoding antisense TGF-β1 into the EMT6 murine mammary tumor cell line using a retroviral vector (Las-TGF-β1SN). EMT6 cells transduced with this vector (EMT6as-TGF-β1 ) stably expressed the antisense gene and secreted 52% less TGF-β than did tumor cells transduced with the backbone vector alone. Supernatant fluid recovered from tumor cells expressing the antisense TGF-β1 gene also exhibited a decreased capacity to inhibit alloantigen-specific cytotoxic T-cell responses in vitro. Furthermore, tumor growth in mice injected with EMT6as-TGF-β1 tumor cells was inhibited compared to mice injected with control tumor cells. These results demonstrate that expression of antisense TGF-β1 by transduced EMT6 cells decreases their tumorigenicity and suggest that this approach of eliminating immune suppression is a potentially useful strategy to enhance antitumor responses.

Original languageEnglish (US)
Pages (from-to)42-50
Number of pages9
JournalCancer gene therapy
Volume4
Issue number1
StatePublished - Dec 1 1997

Keywords

  • Antisense TGF-β
  • Antitumor immunity
  • EMT6 mammary carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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