Retrovirus-mediated transfer of prothymosin gene inhibits tumor growth and prolongs survival in murine bladder cancer

A. L. Shiau, P. R. Lin, M. Y. Chang, C. L. Wu

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

To explore the potential use of prothymosin α(ProT), a putative thymic hormone, in gene therapy for bladder cancer, we generated a replication-defective recombinant retroviral vector encoding ProT and tested its antitumor effect on the MBT-2 murine bladder cancer. C3H/HeN mice injected with MBT-2 cells in conjunction with retroviruses encoding ProT exhibited smaller tumor mass, lower tumor incidence and higher survival rate, as well as higher antitumor cytotoxic activities compared with those injected with control viruses. However, such effects were not observed in severe combined immunodeficiency mice, suggesting that ProT exerts antitumor effects through its immunomodulatory activities. Cell growth in monolayer culture and colony formation in soft agar were enhanced in ProT gene-modified MBT-2 clones, and such growth-promoting activities of ProT could be reversed if its nuclear localization signal (NLS) was deleted. To circumvent the proliferation-promoting effect of ProT on tumor cells, a retroviral vector encoding ProT lacking NLS was constructed. Our results showed that retroviruses encoding NLS-deleted ProT was more efficacious than those encoding wild-type ProT in prolonging survival of tumor-bearing mice. This is the first report indicating that ProT, in particular NLS-deleted ProT, delivered by retroviral vectors may be further explored for the treatment of bladder cancer.

Original languageEnglish
Pages (from-to)1609-1617
Number of pages9
JournalGene Therapy
Volume8
Issue number21
DOIs
Publication statusPublished - 2001 Dec 5

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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