Transcriptional targeting of tumors with a novel tumor-specific survivin promoter

Zeng B. Zhu, Sharmila K. Makhija, Baogen Lu, Minghui Wang, Lioudmila Kaliberova, Bin Liu, Angel A. Rivera, Dirk M. Nettelbeck, Parameshwar J. Mahasreshti, Charles A. Leath, Shannon Barker, Masato Yamaoto, Fengzhi Li, Ronald D. Alvarez, David T. Curiel

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

It has been demonstrated that survivin, a novel member of the inhibitor of apoptosis (IAP) protein family, is expressed in human cancers but is undetectable in normal differentiated tissues. We employed a recombinant adenoviral vector (reAdGL3BSurvivin) in which a tumor-specific survivin promoter and a luciferase reporter gene were inserted into the E1-deleted region of adenovirus vector. Luciferase activity was measured in both multiple tumor cell lines and two primary melanoma cells infected with reAdGL3BSurvivin. Human fibroblast and mammary epithelial cell lines were used as negative controls. A reAdGL3CMV, containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity generated by the survivin promoter. Our data revealed that the survivin promoter showed high activity in both established tumor cell lines and the primary melanoma cells. In contrast, the in vivo studies indicated that the activities of survivin promoter were extremely low in the major mouse organs. The survivin promoter appears to be a promising tumor-specific promoter exhibiting a "tumor on" and "liver off" profile, and therefore, it may prove to be a good candidate for transcriptional targeting of cancer gene therapy in a wide variety of tumors.

Original languageEnglish (US)
Pages (from-to)256-262
Number of pages7
JournalCancer Gene Therapy
Volume11
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

Luciferases
Tumor Cell Line
Melanoma
Neoplasms
Inhibitor of Apoptosis Proteins
Neoplasm Genes
Reporter Genes
Adenoviridae
Genetic Therapy
Carcinogens
Breast
Fibroblasts
Epithelial Cells
Cell Line
Liver
Genes

Keywords

  • Adenoviral vector
  • Survivin gene
  • Transcriptional targeting
  • Tumor-specific promoter

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Transcriptional targeting of tumors with a novel tumor-specific survivin promoter. / Zhu, Zeng B.; Makhija, Sharmila K.; Lu, Baogen; Wang, Minghui; Kaliberova, Lioudmila; Liu, Bin; Rivera, Angel A.; Nettelbeck, Dirk M.; Mahasreshti, Parameshwar J.; Leath, Charles A.; Barker, Shannon; Yamaoto, Masato; Li, Fengzhi; Alvarez, Ronald D.; Curiel, David T.

In: Cancer Gene Therapy, Vol. 11, No. 4, 04.2004, p. 256-262.

Research output: Contribution to journalArticle

Zhu, ZB, Makhija, SK, Lu, B, Wang, M, Kaliberova, L, Liu, B, Rivera, AA, Nettelbeck, DM, Mahasreshti, PJ, Leath, CA, Barker, S, Yamaoto, M, Li, F, Alvarez, RD & Curiel, DT 2004, 'Transcriptional targeting of tumors with a novel tumor-specific survivin promoter', Cancer Gene Therapy, vol. 11, no. 4, pp. 256-262. https://doi.org/10.1038/sj.cgt.7700679
Zhu, Zeng B. ; Makhija, Sharmila K. ; Lu, Baogen ; Wang, Minghui ; Kaliberova, Lioudmila ; Liu, Bin ; Rivera, Angel A. ; Nettelbeck, Dirk M. ; Mahasreshti, Parameshwar J. ; Leath, Charles A. ; Barker, Shannon ; Yamaoto, Masato ; Li, Fengzhi ; Alvarez, Ronald D. ; Curiel, David T. / Transcriptional targeting of tumors with a novel tumor-specific survivin promoter. In: Cancer Gene Therapy. 2004 ; Vol. 11, No. 4. pp. 256-262.
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AB - It has been demonstrated that survivin, a novel member of the inhibitor of apoptosis (IAP) protein family, is expressed in human cancers but is undetectable in normal differentiated tissues. We employed a recombinant adenoviral vector (reAdGL3BSurvivin) in which a tumor-specific survivin promoter and a luciferase reporter gene were inserted into the E1-deleted region of adenovirus vector. Luciferase activity was measured in both multiple tumor cell lines and two primary melanoma cells infected with reAdGL3BSurvivin. Human fibroblast and mammary epithelial cell lines were used as negative controls. A reAdGL3CMV, containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity generated by the survivin promoter. Our data revealed that the survivin promoter showed high activity in both established tumor cell lines and the primary melanoma cells. In contrast, the in vivo studies indicated that the activities of survivin promoter were extremely low in the major mouse organs. The survivin promoter appears to be a promising tumor-specific promoter exhibiting a "tumor on" and "liver off" profile, and therefore, it may prove to be a good candidate for transcriptional targeting of cancer gene therapy in a wide variety of tumors.

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