title: VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN.
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.
authors: Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
authors: Xian
authors: X
authors: Yu
authors: Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan 637007, P.R. China.
authors: Zhengmin
authors: Z
authors: Xu
authors: Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan 637007, P.R. China.
authors: Jun
authors: J
authors: Lei
authors: Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan 637007, P.R. China.
authors: Tingting
authors: T
authors: Li
authors: Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan 637007, P.R. China.
authors: Yan
authors: Y
authors: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D018259:Herpesvirus 1, Human / Q000737:chemistry / Q000235:genetics; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D015678:Viral Structural Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human