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TC21 mediates transformation and cell survival via activation of phosphatidylinositol 3-kinase/Akt and NF-κB signaling pathway

Oncogene volume 21, pages 1062–1070 (2002)Cite this article

Abstract

The signaling pathways of TC21-mediated transformation and cell survival are not well-established. In this study, we have investigated the role of PI3-K/Akt signaling pathway in oncogenic-TC21-mediated transformation and cell survival. We found that oncogenic-TC21 stimulated the PI3-K activity. This was associated with the activation of Akt, a key component of PI3-K signaling pathway. We also found that TC21 interacted and formed complex with PI3-K. Mutations in the GTP-binding region of TC21, which enhanced GTP-binding potential of this protein, also stimulated its association with PI3-K, suggesting that PI3-K may preferentially interact with the GTP-bound form. Suppression of PI3-K and Akt by specific inhibitors LY294002 and Wortmannin reversed TC21-induced transformation. Likewise, inhibition of PI3-K activity by the PI3-K phosphotase PTEN reduced TC21-mediated focus formation in NIH3T3 cells. Investigation of TC21's effect on cell survival revealed that mutant-TC21 expressing cells were more resistant to etoposide- and cisplatin-induced cell death, and this was associated with the activation of anti-apoptotic protein NF-κB, a downstream target of Akt. Treatment of PI3-K inhibitor LY294002 significantly suppressed TC21-mediated NF-κB activation. In conclusion, we have identified PI3-K as an effector of TC21 and demonstrated that the PI3-K/Akt signaling pathway plays important roles in TC21-mediated transformation and cell survival.

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Authors and Affiliations

  1. Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, 13210, NY, USA

    Rong Rong, Qin He, M Saeed Sheikh & Ying Huang

  2. Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, 21224, Maryland, MD, USA

    Yusen Liu

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  1. Rong Rong
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Correspondence to Ying Huang.

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Rong, R., He, Q., Liu, Y. et al. TC21 mediates transformation and cell survival via activation of phosphatidylinositol 3-kinase/Akt and NF-κB signaling pathway. Oncogene 21, 1062–1070 (2002). https://doi.org/10.1038/sj.onc.1205154

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