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Induction of p53-regulated genes in lung cancer cells: implications of the mechanism for adenoviral p53-mediated apoptosis

Oncogene volume 23, pages 1300–1307 (2004)Cite this article

Abstract

The p53 gene is the most frequently mutated gene in human cancers. Loss of functional p53 leads to impaired responses of cancer cells to apoptosis induction and to poor prognosis in patients with certain types of cancer. Cancer gene therapies using ectopic expression of wild-type p53 to force cancer cells through the apoptotic pathway have been tested extensively preclinically and clinically, and genes in various cell lines have been reported to be regulated upon ectopic p53 overexpression. However, the effect of p53 on many other p53-dependent and apoptosis-related genes remains unclear, as does the mechanism of p53-induced apoptosis in human cancers. In this study, we used real-time reverse transcription polymerase chain reaction to evaluate the changes in expression of various p53-dependent and apoptosis-related genes in five human non-small-cell lung cancer cell lines with varying p53 statuses after adenoviral p53 treatment. We found that Ad/p53 induced the expression of the proapoptotic genes PUMA, Bak, Bax, and Fas in a cell type- and time-dependent manner. Among these genes, PUMA was upregulated the most dramatically and broadly. However, when a specific siRNA construct against PUMA was employed, we observed no attenuation of apoptosis in H1299 cells. Our data suggest that Ad-p53 induces the expression of a variety of proapoptotic genes and that lack of induction in one of these genes does not block Ad/p53-mediated cell killing in human lung cancer cells.

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Acknowledgements

We thank Allan Prejusa and Henry Peng in the Keck Vector Core for adenovirus propagation and quality control, Gayle Nesom for editorial review and Alma Vega for assistance in preparing the manuscript. This work was supported in part by NCI grants (RO1 CA 092487-01A1 and RO1 CA 098582-01A1 to BF; PO1 CA78778-01A1 and Lung Cancer SPORE 2P50-CA70970-04 to JAR); an NIH Core Grant for Medium and Vectors (CA 16672); and a grant from the WM Keck Foundation. JG is an MD Anderson Odyssey Program Fellow supported by the Theodore N Law Endowment for Scientific Achievement.

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  1. Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Jian Gu, Lidong Zhang, Stephen G Swisher, Jack A Roth & Bingliang Fang

  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    Jinsong Liu

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  1. Jian Gu
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Correspondence to Bingliang Fang.

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Gu, J., Zhang, L., Swisher, S. et al. Induction of p53-regulated genes in lung cancer cells: implications of the mechanism for adenoviral p53-mediated apoptosis. Oncogene 23, 1300–1307 (2004). https://doi.org/10.1038/sj.onc.1207239

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