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Updated: May 17, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Molecularly modified VP3 (30-121) induces apoptosis in human bladder cancer (EJ) cells but not in normal (3T3) cells
Junfeng Yang1, Jiansong Wang, Yigang Zuo
1Department of Urology, The Second Affiliated Hospital Of Kunming Medical University, Kunming, Yunnan 650101, People's Republic of China.
Abstract:
The chicken anaemia virus protein 3 (VP3 or apoptin) induces apoptosis specifically in tumour and transformed cells but not in normal cells. This selective apoptosis is ideal for therapeutic purposes. However, VP3, a heterologous protein, is immunogenic in vivo. Such a drawback limits its clinical usage. To diminish its potential immunogenicity, we modified the sequence of VP3. The VP3 genes functional sequence starts at 33 AA (amino acids) from the N-terminal side, and the first protein structural domain consists of 30 AA. We found that the first domain of VP3 contains no functional sequences. Therefore, this domain was removed to test whether its absence affects apoptosis. Transfection of EGFP (enhance green fluorescent protein)-modified-VP3 or HA-modified-VP3 in bladder cancer cell lines (EJ) resulted in its expression, successful localization to the nucleus and efficient induction of apoptosis. Expression of EGFP-modified-VP3 or HA-modified-VP3 had no influence on mouse fibroblast cells (3T3). The modified VP3 (30-121), like the wild-type VP3, induced EJ cell apoptosis without affecting 3T3 cells. This study increases our understanding of modified VP3 (30-121) as a possible substitute for the wild-type VP3, which makes VP3 (30-121) an interesting candidate for the development of novel therapeutic strategies.
Insights
Modified chicken anemia virus protein 3 (VP3) selectively induces apoptosis in cancer cells without affecting normal cells. This VP3 (30-121) modification reduces immunogenicity, offering a promising therapeutic candidate.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Chicken anemia virus protein 3 (VP3), also known as apoptin, selectively induces apoptosis in tumor cells.
- VP3's therapeutic potential is limited by its in vivo immunogenicity.
- The functional sequence of VP3 begins at amino acid 33, with the first 30 amino acids forming a non-functional domain.
Purpose of the Study:
- To investigate the potential of a modified VP3 (VP3 (30-121)) with a removed N-terminal domain to retain its tumor-selective apoptotic activity.
- To assess if removing the non-functional N-terminal domain reduces VP3's immunogenicity.
Main Methods:
- VP3 gene was modified by deleting the first 30 amino acids.
- EGFP-modified-VP3 and HA-modified-VP3 were transfected into bladder cancer cell lines (EJ) and mouse fibroblast cells (3T3).
- Apoptosis induction, protein expression, and subcellular localization were analyzed.
Main Results:
- Modified VP3 (30-121) was successfully expressed and localized to the nucleus in EJ cells.
- VP3 (30-121) efficiently induced apoptosis in EJ bladder cancer cells.
- Expression of modified VP3 did not affect the viability of normal mouse fibroblast cells (3T3).
Conclusions:
- The modified VP3 (30-121) retains its ability to selectively induce apoptosis in cancer cells while sparing normal cells.
- VP3 (30-121) represents a promising candidate for developing novel cancer therapeutics with reduced immunogenicity.
