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p21WAF1/CIP1 is more effective than p53 in growth suppression of mouse renal carcinoma cell line Renca in vitro and in vivo

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Abstract

Purpose

Although there are many controversial reports about the effect of p53 and p21WAF1/CIP1 overexpression in different human tumor cells, the p53 gene is shown to be a more effective candidate for cancer gene therapy because of its more pronounced ability to induce apoptosis. In the present study, we present the effect of p53 and p21WAF1/CIP1 overexpression on mouse renal carcinoma cells in vitro and in vivo.

Methods

p53 and p21WAF1/CIP1 genes were introduced into Renca cells using adenoviral vectors (Ad5CMV-p53 and Ad5CMV-p21). The induction of apoptosis was measured using Annexin V assay and DNA fragmentation analysis. The expression of proteins was examined using immunocytochemistry and Western blot methods. The ability of adenoviral vectors to inhibit tumorigenicity of Renca cells, as well as the growth of pre-established tumors was measured.

Results

In vitro growth assays revealed higher growth suppression after Ad5CMV-p21 infection. Although both vectors induced apoptosis, Ad5CMV-p53 was slightly more efficient. In vivo studies in Balb/c mice, demonstrated that tumorigenicity was completely suppressed by Ad5CMV-p21. Besides this, Ad5CMV-p21 significantly inhibited the growth of established tumors, while Ad5CMV-p53 did not.

Conclusions

These data suggest that p21WAF1/CIP1 is a more potent growth suppressor than p53 of mouse tumor cells Renca. The divergent responses of tumor cells to p21WAF1/CIP1 overexpression could be due to various networks that differ between species.

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Acknowledgement

This work was supported by grant 0098092 from the Ministry of Science and Technology, Republic of Croatia. We thank Mihaela Alivojvodić for expert technical assistance, and Dr. Anđelko Hrženjak and Dr. Saša Frank for useful discussions.

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Authors and Affiliations

  1. Division of Molecular Medicine, Rudjer Bošković Institute, Bijenička c. 54, P.O.Box 180, 10002, Zagreb, Croatia

    Marijeta Kralj & Jasminka Pavelić

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  1. Marijeta Kralj
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  2. Jasminka Pavelić
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Correspondence to Marijeta Kralj.

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Kralj, M., Pavelić, J. p21WAF1/CIP1 is more effective than p53 in growth suppression of mouse renal carcinoma cell line Renca in vitro and in vivo. J Cancer Res Clin Oncol 129, 463–471 (2003). https://doi.org/10.1007/s00432-003-0458-2

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  • DOI: https://doi.org/10.1007/s00432-003-0458-2

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