A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors

Chia Ling Hsieh, Haiyen E. Zhau, Leland W K Chung, Ling Yang, Li Miao, Fang Yeung, Chinghai Kao, Hua Yang

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40 Citations (Scopus)

Abstract

We report the development of a novel replication-competent adenoviral vector, Ad-hOC-E1, containing a single bidirectional human osteocalcin (hOC) promoter to drive both the early viral E1A and E1B gene. This vector selectively replicated in OC-expressing but not non-OC-expressing cells, with viral replication enhanced at least 10-fold on vitamin D3 exposure. Both the artificial TATA-box and hOC promoter element in this bidirectional promoter construct were controlled by a common OC regulatory element which selectively activated OC expression in cells. The expression of E1A and E1B gene by Ad-hOC-E1 can be markedly induced by vitamin D3. Unlike Ad-sPSA-E1, an adenoviral vector with viral replication controlled by a strong super prostate-specific antigen (sPSA) promoter which only replicates in PSA-expressing cells with androgen receptor (AR), Ad-hOC-E1 retarded the growth of both androgen-dependent and androgen-independent prostate cancer cells irrespective of their basal level of AR and PSA expression. A single i.v. administration of 2 × 109 plaque-forming units of Ad-hOC-E1 inhibited the growth of previously established s.c. DU145 tumors (an AR- and PSA-negative cell line). Viral replication is highly enhanced by i.p. administration of vitamin D3. Ultimately, enhancing Ad-hOC-E1 viral replication by vitamin D3 may be used clinically to treat localized and osseous metastatic prostate cancer in men.

Original languageEnglish
Pages (from-to)3084-3092
Number of pages9
JournalCancer Research
Volume62
Issue number11
Publication statusPublished - Jun 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Hsieh, C. L., Zhau, H. E., Chung, L. W. K., Yang, L., Miao, L., Yeung, F., Kao, C., & Yang, H. (2002). A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors. Cancer Research, 62(11), 3084-3092.