Suppression of lung cancer with siRNA targeting PTTG

  • Authors:
    • Sham S. Kakar
    • Mohammad T. Malik
  • View Affiliations

  • Published online on: August 1, 2006     https://doi.org/10.3892/ijo.29.2.387
  • Pages: 387-395
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Abstract

Pituitary transforming gene (PTTG) is frequently expressed at high levels in malignant tumors. We report high levels of expression of PTTG in various lung tumors and tumor-derived cell lines. For a better understanding of its role in maintaining the cancer phenotype, we used RNA interference (RNAi) directed against PTTG. Transfection of H1299 cells with PTTG siRNA duplex (5'-UGG GAG AUC UCA AGU UUC A-3') to a final concentration of 100 nmol/l resulted in almost complete depletion of PTTG mRNA within 24 and 48 h when compared to expression in untransfected cells or cells transfected with control siRNA. Western blot analysis showed nearly a 60% reduction in PTTG protein within 48 h of transfection. In phenotype analysis, we investigated the effect of PTTG siRNA on colony formation on soft agar, and tumor development in nude mice. Transfection of H1299 cells with PTTG siRNA duplex significantly reduced colony formation compared to untransfected cells or cells transfected with control siRNA. Mice injected with H1299 cells transfected with PTTG siRNA followed by injection of siRNA developed no tumors within two weeks of injection, but developed small tumors (67.85±45.87 mg) within 4 weeks of injection, whereas untransfected cells, or cells transfected with control siRNA developed large tumors (232.12±102.78 and 231.57±83.76 mg respectively). Suppression of PTTG as well as Ki67, bFGF and CD34 was observed in H1299 tumors treated with PTTG siRNA compared to untreated and control-treated siRNA in nude mice. In conclusion, decreasing PTTG expression through PTTG siRNA inhibits tumor growth both in vitro and in vivo. Future studies are needed to test whether PTTG expression can be efficiently depleted by siRNA expressed from a DNA-based expression vector combined with a specific-promoter, such that RNAi can specifically target PTTG in cancer cells without affecting normal cells.

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August 2006
Volume 29 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kakar SS and Malik MT: Suppression of lung cancer with siRNA targeting PTTG. Int J Oncol 29: 387-395, 2006.
APA
Kakar, S.S., & Malik, M.T. (2006). Suppression of lung cancer with siRNA targeting PTTG. International Journal of Oncology, 29, 387-395. https://doi.org/10.3892/ijo.29.2.387
MLA
Kakar, S. S., Malik, M. T."Suppression of lung cancer with siRNA targeting PTTG". International Journal of Oncology 29.2 (2006): 387-395.
Chicago
Kakar, S. S., Malik, M. T."Suppression of lung cancer with siRNA targeting PTTG". International Journal of Oncology 29, no. 2 (2006): 387-395. https://doi.org/10.3892/ijo.29.2.387