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

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E-ISSN： 1791-3004|12|1|1286-1290

ISSN： 1791-2997

Source： Molecular Medicine Reports, Vol.12, Iss.1, 2015-01, pp. : 1286-1290

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Abstract

PTEN acts as a phosphatidylinositol phosphatase with a possible role in the phosphatidylinositol 3kinase (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 noncutaneous 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 HSV1VP22 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 Cterminal PTENVP22 fusion proteins were constructed. VP22mediated intercellular transport and antitumor efficacy in BT549 (PTENnull) breast tumor cells were investigated. The results showed that PTENVP22 has the same spreading abilities as VP22. In cell proliferation and apoptosis assays, PTENVP22 gene transfer induces a stronger antiproliferative effect and apoptotic activity compared with PTEN gene transfer alone. In addition, VP22 enhanced the PTENmediated decrease in the level of phosphorylated AKT. The results show that PTENVP22 can spread in vitro and PTENVP22 gene induces significantly greater antitumor activity than the PTEN gene alone. This study confirms the utility of VP22mediated delivery in vitro and suggests that PTENVP22 may have applications in breast cancer gene therapy.