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 | Xian Yu, Zhengmin Xu, Jun Lei, Tingting Li, Yan Wang |
Journal | Molecular medicine reports
(Mol Med Rep)
Vol. 12
Issue 1
Pg. 1286-90
(Jul 2015)
ISSN: 1791-3004 [Electronic] Greece |
PMID | 25816150
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Recombinant Fusion Proteins
- Viral Structural Proteins
- herpes simplex virus type 1 protein VP22
- Proto-Oncogene Proteins c-akt
- PTEN Phosphohydrolase
- PTEN protein, human
|
Topics |
- Apoptosis
(genetics)
- Cell Line, Tumor
- Female
- Gene Expression Regulation, Neoplastic
- Gene Transfer Techniques
- Genetic Therapy
(methods)
- Herpesvirus 1, Human
(chemistry, genetics)
- Humans
- Mammary Glands, Human
(metabolism, pathology)
- Molecular Targeted Therapy
(methods)
- PTEN Phosphohydrolase
(genetics, metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(antagonists & inhibitors, genetics, metabolism)
- Recombinant Fusion Proteins
- Signal Transduction
- Viral Structural Proteins
(genetics, metabolism)
|