Abstract
Unlike normal mucosal squamous epithelial cells, head and neck squamous cell carcinomas (HNSCCs) overexpress TGF-α mRNA and protein which is required to sustain the proliferation of HNSCC cells in vitro. To determine whether TGF-α expression contributes to tumor growth in vivo, cationic liposome-mediated gene transfer was used to deliver an antisense expression construct targeting the human TGF-α gene into human head and neck tumor cells, grown as subcutaneous xenografts in nude mice. The TGF-α anti-sense gene was immediately detected in the cytoplasm of the tumor cells, translocated to the nucleus by 12 h and remained localized to the nucleus for up to 3 days. Direct inoculation of the TGF-α antisense (but not the corresponding sense) construct into established HNSCC tumors resulted in inhibition of tumor growth. Sustained antitumor effects were observed for up to 1 year after the treatments were discontinued. Down-modulation of TGF-α was accompanied by increased apoptosis in vivo. These experiments indicate that interference with the TGF-α/EGFR autocrine signaling pathway may be an effective therapeutic strategy for cancers which overexpress this ligand/receptor pair.
Original language | English (US) |
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Pages (from-to) | 1906-1914 |
Number of pages | 9 |
Journal | Gene Therapy |
Volume | 7 |
Issue number | 22 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
Keywords
- Head and neck cancer
- Transforming growth factor alpha
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics