The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines

Xue Yan Peng, Jong Ho Won, Thomas Rutherford, Takuma Fujii, Daniel Zelterman, Giuseppi Pizzorno, Eva Sapi, John Leavitt, Barry Kacinski, Ronald Crystal, Peter Schwartz, Albert Deisseroth

Research output: Contribution to journalArticle

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Abstract

A 2.4-kh truncated L-plastin promoter was inserted either 5′ to the LacZ gene (Ad-Lp-LacZ) or 5′ to the cytosine deaminase (CD) gene (Ad-Lp-CD) in a replication-incompetent adenoviral vector backbone. Infectivity and cytotoxicity experiments with the LacZ and CD vectors suggested that the L-plastin promoter-driven transcriptional units were expressed at much higher levels in explants of ovarian cancer cells from patients and in established ovarian or bladder cancer cell lines than they were in normal peritoneal mesothelial cells from surgical specimens, in organ cultures of normal ovarian cells, or in the established CCD minimal deviation fibroblast cell line. Control experiments showed that this difference was not attributable to the lack of infectivity of the normal peritoneal cells, the normal ovarian cells, or the minimal deviation CCD fibroblast cell line, because these cells showed expression of the LacZ reporter gene when exposed to the replication-incompetent adenoviral vector carrying the cytomegalovirus (CMV)-driven LacZ gene (Ad-CMV-LacZ). The Ovcar-5 and Skov-3 ovarian cancer cell lines exposed to the Ad-Lp-CD adenoviral vector were much more sensitive to the prodrug 5-fluorocytosine (5FC), which is converted from the 5FC prodrug into the toxic chemical 5-fluorouracil, than was the CCD minimal deviation fibroblast cell line after exposure to the same vector. A mouse xenograft model was used to show that the Ad-Lp-CD vector/5FC system could prevent engraftment of ovarian cancer cells in nude mice. Finally, injection of the Ad-Lp-CD vector into s.c. tumor nodules generated a greater reduction of the size of the tumor nodules than did injection of the Ad-CMV-LacZ vectors into tumor nodules. The Ad-Lp-CD vectors were as suppressive to tumor growth as the Ad-CMV-CD vectors. These results suggest that an adenoviral vector carrying the CD gene controlled by the L-plastin promoter (Ad-Lp-CD) may be of potential value for the i.p. therapy of ovarian cancer.

Original languageEnglish
Pages (from-to)4405-4413
Number of pages9
JournalCancer Research
Volume61
Issue number11
Publication statusPublished - 1 Jun 2001
Externally publishedYes

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Cytosine Deaminase
Urinary Bladder Neoplasms
Ovarian Neoplasms
Gene Expression
Cell Line
Neoplasms
Cytomegalovirus
Flucytosine
Lac Operon
Fibroblasts
Prodrugs
plastin
Injections
Poisons
Organ Culture Techniques
Reporter Genes
Heterografts
Nude Mice
Fluorouracil
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Peng, X. Y., Won, J. H., Rutherford, T., Fujii, T., Zelterman, D., Pizzorno, G., ... Deisseroth, A. (2001). The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines. Cancer Research, 61(11), 4405-4413.

The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines. / Peng, Xue Yan; Won, Jong Ho; Rutherford, Thomas; Fujii, Takuma; Zelterman, Daniel; Pizzorno, Giuseppi; Sapi, Eva; Leavitt, John; Kacinski, Barry; Crystal, Ronald; Schwartz, Peter; Deisseroth, Albert.

In: Cancer Research, Vol. 61, No. 11, 01.06.2001, p. 4405-4413.

Research output: Contribution to journalArticle

Peng, XY, Won, JH, Rutherford, T, Fujii, T, Zelterman, D, Pizzorno, G, Sapi, E, Leavitt, J, Kacinski, B, Crystal, R, Schwartz, P & Deisseroth, A 2001, 'The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines', Cancer Research, vol. 61, no. 11, pp. 4405-4413.
Peng XY, Won JH, Rutherford T, Fujii T, Zelterman D, Pizzorno G et al. The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines. Cancer Research. 2001 Jun 1;61(11):4405-4413.
Peng, Xue Yan ; Won, Jong Ho ; Rutherford, Thomas ; Fujii, Takuma ; Zelterman, Daniel ; Pizzorno, Giuseppi ; Sapi, Eva ; Leavitt, John ; Kacinski, Barry ; Crystal, Ronald ; Schwartz, Peter ; Deisseroth, Albert. / The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines. In: Cancer Research. 2001 ; Vol. 61, No. 11. pp. 4405-4413.
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