Novel prostate-specific promoter derived from PSA and PSMA enhancers

Sang Jin Lee, Hong Sup Kim, Rong Yu, KangRyul Lee, Thomas Gardner, Chaeyong Jung, Meei Huey Jeng, Fan Yeung, Liang Cheng, Chinghai Kao

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The expression of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA), two well characterized marker proteins, remains highly active in the hormone refractory stage of prostate cancer. In this study, an artificial chimeric enhancer (PSES) composed of two modified regulatory elements controlling the expression of PSA and PSMA genes was tested for its promoter activity and tissue specificity using the reporter system. As a result, this novel PSES promoter remained silent in PSA- and PSMA-negative prostate and non-prostate cancer cell lines, but mediated high levels of luciferase in PSA- and PSMA-expressing prostate cancer cell lines in the presence and absence of androgen. To determine whether PSES could be used for in vivo gene therapy of prostate cancer, a recombinant adenovirus, Ad-PSES-luc, was constructed. Luciferase activity in prostate cancer cell lines mediated by Ad-PSES-luc was 400- to 1000-fold higher than in several other non-prostate cell lines, suggesting the high tissue-specificity of the PSES promoter in an adenoviral vector. Finally, recombinant virus Ad-PSES-luc was injected into mice to evaluate the tissue-discriminatory promoter activity in an experimental animal. Unlike Ad-CMV-luc, the luciferase activity from systemic injection of Ad-PSES-luc was fairly low in all major organs. However, when injected into prostate, Ad-PSES-luc drove high luciferase activity almost exclusively in prostate and not in other tissues. Our results demonstrated the potential use of PSES for the treatment of androgen-independent prostate cancer patients.

Original languageEnglish
Pages (from-to)415-421
Number of pages7
JournalMolecular Therapy
Volume6
Issue number3
DOIs
StatePublished - Sep 1 2002

Fingerprint

Prostate-Specific Antigen
Prostate
Prostatic Neoplasms
Luciferases
Cell Line
Organ Specificity
Androgens
Adenoviridae
Genetic Therapy
human glutamate carboxypeptidase II
Hormones
Viruses
Injections
Genes
Neoplasms
Proteins
Therapeutics

Keywords

  • Adenovirus
  • Gene therapy
  • Prostate
  • PSA
  • PSMA

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Novel prostate-specific promoter derived from PSA and PSMA enhancers. / Lee, Sang Jin; Kim, Hong Sup; Yu, Rong; Lee, KangRyul; Gardner, Thomas; Jung, Chaeyong; Jeng, Meei Huey; Yeung, Fan; Cheng, Liang; Kao, Chinghai.

In: Molecular Therapy, Vol. 6, No. 3, 01.09.2002, p. 415-421.

Research output: Contribution to journalArticle

Lee, Sang Jin ; Kim, Hong Sup ; Yu, Rong ; Lee, KangRyul ; Gardner, Thomas ; Jung, Chaeyong ; Jeng, Meei Huey ; Yeung, Fan ; Cheng, Liang ; Kao, Chinghai. / Novel prostate-specific promoter derived from PSA and PSMA enhancers. In: Molecular Therapy. 2002 ; Vol. 6, No. 3. pp. 415-421.
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