VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN

  • Authors:
    • Xian Yu
    • Zhengmin Xu
    • Jun Lei
    • Tingting Li
    • Yan Wang
  • View Affiliations

  • Published online on: March 18, 2015     https://doi.org/10.3892/mmr.2015.3509
  • Pages: 1286-1290
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Abstract

PTEN acts as a phosphatidylinositol phosphatase with a possible role in the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway. Mutations in PTEN are frequent and their presence is associated with poor prognosis in breast cancer, which is the most common type of non‑cutaneous malignancy in females. Delivery of the tumor suppressor PTEN gene represents a powerful strategy for breast cancer therapy, but a present limitation of gene therapy is the ability to deliver sufficient quantities of active proteins to target cells. The capacity of HSV‑1VP22 fusion proteins to spread from the primary transduced cell to surrounding cells could improve gene therapeutics, particularly in cancer. To assess the potential efficacy of VP22 as a gene therapy for breast cancer, expression vectors for N‑ and C‑terminal PTEN‑VP22 fusion proteins were constructed. VP22‑mediated intercellular transport and antitumor efficacy in BT549 (PTEN‑null) breast tumor cells were investigated. The results showed that PTEN‑VP22 has the same spreading abilities as VP22. In cell proliferation and apoptosis assays, PTEN‑VP22 gene transfer induces a stronger anti‑proliferative effect and apoptotic activity compared with PTEN gene transfer alone. In addition, VP22 enhanced the PTEN‑mediated decrease in the level of phosphorylated AKT. The results show that PTEN‑VP22 can spread in vitro and PTEN‑VP22 gene induces significantly greater antitumor activity than the PTEN gene alone. This study confirms the utility of VP22‑mediated delivery in vitro and suggests that PTEN‑VP22 may have applications in breast cancer gene therapy.
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July-2015
Volume 12 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yu X, Xu Z, Lei J, Li T and Wang Y: VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN. Mol Med Rep 12: 1286-1290, 2015
APA
Yu, X., Xu, Z., Lei, J., Li, T., & Wang, Y. (2015). VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN. Molecular Medicine Reports, 12, 1286-1290. https://doi.org/10.3892/mmr.2015.3509
MLA
Yu, X., Xu, Z., Lei, J., Li, T., Wang, Y."VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN". Molecular Medicine Reports 12.1 (2015): 1286-1290.
Chicago
Yu, X., Xu, Z., Lei, J., Li, T., Wang, Y."VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN". Molecular Medicine Reports 12, no. 1 (2015): 1286-1290. https://doi.org/10.3892/mmr.2015.3509