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| Original Paper |
| Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells |
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| Tongyu Lin1,a, Xuefeng Huang1, Jian Gu1, Lidong Zhang1, Jack A Roth1, Momiao Xiong2, Steven A Curley3, Yinhua Yu4, Kelly K Hunt3 and Bingliang Fang1 |
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1Department of Thoracic and Cardiovascular Surgery, Section of Thoracic Molecular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, TX 77030, USA
2Human Genetics Center, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, TX 77030, USA
3Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, TX 77030, USA
4Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, TX 77030, USA
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Correspondence to: B Fang, Department of Thoracic and Cardiovascular Surgery, Unit 445, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas, TX 77030, USA; E-mail: Bfang@notes.mdacc.tmc.edu | |
aCurrent address: Cancer Center, Sun Yat-sen University, Guangzhou 510060, China |
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| Abstract |
| We evaluated anti-tumor activity and toxic effect of an adenoviral vector expressing the GFP/TRAIL fusion gene from the hTERT promoter (designated Ad/gTRAIL) on human breast cancer cell lines and on normal human breast cells. Treatment with Ad/gTRAIL elicited high levels of transgene expression and apoptosis in a variety of breast cancer cell lines. Furthermore, treatment with Ad/gTRAIL was effective in killing breast cancer lines resistant to doxorubicin or soluble TRAIL protein. In contrast, only minimal transgene expression and toxicity was detected in normal human primary mammary epithelial cells after treatment with this vector. An in vivo study further showed that the intralesional administration of Ad/gTRAIL effectively suppressed the growth of human tumor xenografts derived from both doxorubicin-sensitive and doxorubicin-resistant breast cancer lines. Specifically, about 50% of animals bearing doxorubicin-sensitive and doxorubicin-resistant breast cancer xenografts showed complete tumor regression and remained tumor-free for over 5 months. These results suggest that the adenovirus encoding the GFP/TRAIL gene driven by the hTERT promoter has potential application in cancer therapy. Oncogene (2002) 21, 8020-8028. doi:10.1038/sj.onc.1205926 |
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| Keywords |
| apoptosis; drug-resistance; telomerase; doxorubicin; gene therapy |
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| Received 6 June 2002; revised 31 July 2002; accepted 1 August 2002 |
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| 14 November 2002, Volume 21, Number 52, Pages 8020-8028 |
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