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Expression of Concern: Adenovirus‐mediated expression of truncated E2F‐1 suppresses tumor growth in vitro and in vivo
Author(s) -
GomezGutierrez Jorge G.,
GarciaGarcia Aracely,
Hao Hongying,
Rao XiaoMei,
Montes de OcaLuna Roberto,
Zhou Heshan S.,
McMasters Kelly M.
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25322
Subject(s) - in vivo , apoptosis , e2f , transactivation , cancer research , cancer cell , melanoma , cell cycle , genetic enhancement , in vitro , cell culture , cell growth , cancer , biology , medicine , microbiology and biotechnology , gene expression , gene , biochemistry , genetics
BACKGROUND: Adenovirus (Ad)‐mediated E2F‐1 gene transfer induces apoptosis in cancer cells in vitro and in vivo, but clinical application of E2F‐1 in cancer gene therapy remains controversial because of the oncogenic potential of E2F‐1. This barrier can be circumvented by using the truncated form of the E2F‐1 gene (E2Ftr) (amino acids 1 through 375), which lacks the E2F‐1 transactivation domain and cell cycle‐promoting effects. METHODS: The authors constructed 3 adenoviral vectors that expressed E2Ftr under regulation of the tetracycline (Tet)‐off system (AdTet‐E2Ftr1, AdTet‐E2Ftr2, and AdTet‐E2Ftr3). These vectors were compared for E2Ftr expression and apoptosis induction in cancer cells and normal cells. E2Ftr antitumor activity in vivo also was assessed in a melanoma xenograft model. RESULTS: One of the 3 vectors, AdTet‐E2Ftr3, had the highest E2Ftr protein expression levels, which were correlated with the greatest induction of apoptosis and inhibition of cancer cell growth. E2Ftr induced apoptosis in a variety of cancer cell lines independent of p53 status with little cytotoxicity in normal cell lines. In a mouse melanoma xenograft model, AdTet‐E2Ftr3 exhibited an approximately 80% decrease in tumor size compared with controls in vivo. CONCLUSIONS: The current results indicated that AdTet‐E2Ftr3 is a novel anticancer agent that has significant therapeutic activity in vitro and in vivo. Cancer 2010. © 2010 American Cancer Society.