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Long-term tumor-free survival from treatment with the GFP–TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells

Oncogene volume 21, pages 8020–8028 (2002)Cite this article

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.

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Acknowledgements

We thank Allan Prejusa and Trupti Mehta in the Keck Vector Core for adenovirus propagation and quality control and Beth Notzon for editorial review. This work was supported in part by an NCI grant (RO1 CA 092487-01A1 to B Fang); an Institutional Start-Up Fund (B Fang); and a NIH Core Grant (CA16672). J Gu is an M. D. Anderson Cancer Center Odyssey Program Fellow supported by the Kimberly-Clark Endowment for New and Innovative Research.

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Author notes

  1. Tongyu Lin

    Present address: Cancer Center, Sun Yat-sen University, Guangzhou, 510060, China

Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, Section of Thoracic Molecular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Tongyu Lin, Xuefeng Huang, Jian Gu, Lidong Zhang, Jack A Roth & Bingliang Fang

  2. Human Genetics Center, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Momiao Xiong

  3. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Steven A Curley & Kelly K Hunt

  4. Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Yinhua Yu

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Correspondence to Bingliang Fang.

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Lin, T., Huang, X., Gu, J. et al. Long-term tumor-free survival from treatment with the GFP–TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells. Oncogene 21, 8020–8028 (2002). https://doi.org/10.1038/sj.onc.1205926

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