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

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

Research output: Contribution to journalArticle

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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 (US)
Pages (from-to)3084-3092
Number of pages9
JournalCancer Research
Volume62
Issue number11
StatePublished - Jun 1 2002

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Cholecalciferol
Osteocalcin
Androgens
Prostatic Neoplasms
Neoplasms
Androgen Receptors
Prostate-Specific Antigen
TATA Box
Growth
Genes
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors. / Hsieh, Chia Ling; Yang, Ling; Miao, Li; Yeung, Fang; Kao, Chinghai; Yang, Hua; Zhau, Haiyen E.; Kao, Chinghai.

In: Cancer Research, Vol. 62, No. 11, 01.06.2002, p. 3084-3092.

Research output: Contribution to journalArticle

Hsieh, CL, Yang, L, Miao, L, Yeung, F, Kao, C, Yang, H, Zhau, HE & Kao, C 2002, 'A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors', Cancer Research, vol. 62, no. 11, pp. 3084-3092.
Hsieh, Chia Ling ; Yang, Ling ; Miao, Li ; Yeung, Fang ; Kao, Chinghai ; Yang, Hua ; Zhau, Haiyen E. ; Kao, Chinghai. / A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors. In: Cancer Research. 2002 ; Vol. 62, No. 11. pp. 3084-3092.
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