Abstract |
Unlike normal mucosal squamous epithelial cells, head and neck squamous cell carcinomas (HNSCCs) overexpress TGF-alpha mRNA and protein which is required to sustain the proliferation of HNSCC cells in vitro. To determine whether TGF-alpha expression contributes to tumor growth in vivo, cationic liposome-mediated gene transfer was used to deliver an antisense expression construct targeting the human TGF-alpha gene into human head and neck tumor cells, grown as subcutaneous xenografts in nude mice. The TGF-alpha antisense 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-alpha 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-alpha was accompanied by increased apoptosis in vivo. These experiments indicate that interference with the TGF-alpha/EGFR autocrine signaling pathway may be an effective therapeutic strategy for cancers which overexpress this ligand/receptor pair.
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Authors | S Endo, Q Zeng, N A Burke, Y He, M F Melhem, S F Watkins, M N Lango, S D Drenning, L Huang, J Rubin Grandis |
Journal | Gene therapy
(Gene Ther)
Vol. 7
Issue 22
Pg. 1906-14
(Nov 2000)
ISSN: 0969-7128 [Print] England |
PMID | 11127578
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Oligonucleotides, Antisense
- Transforming Growth Factor alpha
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Topics |
- Animals
- Apoptosis
- Carcinoma, Squamous Cell
(therapy)
- Cell Division
- Cell Line
- Gene Expression
- Genetic Therapy
(methods)
- Head and Neck Neoplasms
(therapy)
- Humans
- Mice
- Mice, Nude
- Microscopy, Fluorescence
- Neoplasms, Experimental
(therapy)
- Oligonucleotides, Antisense
(administration & dosage)
- Random Allocation
- Transfection
(methods)
- Transforming Growth Factor alpha
(genetics)
- Xenograft Model Antitumor Assays
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