Identification of tissue- and cancer-selective promoters for the introduction of genes into human ovarian cancer cells

Janos L. Tanyi, Ruth Lapushin, Astrid Eder, Nelly Auersperg, Fazal H. Tabassam, Jack A. Roth, Jian Gu, Binglian Fang, Gordon Mills, Judith Wolf

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective. One potential limitation of gene therapy for epithelial tumors is the lack of tissue or tumor specificity of treatment. Tumor-selective expression of gene therapies may avoid deleterious side effects and improve the efficacy of the treatment. The aim of this study was to evaluate the tissue and tumor specificity of four different potential gene therapy promoters, to determine their usefulness in tissue-specific gene therapy of epithelial ovarian carcinomas. Methods. Three potential epithelial cell-selective (hESE1, SLP1, OSP1) and one potential tumor-selective (hTERT) promoter were placed upstream of a luciferase construct to determine relative activity in a wide variety of normal and malignant cell lines. Transient transfection and luciferase assays were carried out in 12 epithelial ovarian (3 SV40 T antigen-transfected normal and 9 malignant) and 8 control cell lines. Results. Luciferase assays revealed that the hTERT promoter presented the highest tumor selectivity, hESE1 and SLP1 promoters showed strong epithelial cell selectivity (hESE1, 16/17; SLP1, 15/17), with the OSP1 (11/17) promoter exhibiting lower epithelial selectivity. Of the potential promoters for gene therapy, hTERT promoter exhibited the strongest transcriptional activity in most of the tumor cell lines. None of the promoters exhibited strict ovarian epithelium selectivity. Conclusion. The hTERT promoter may be an optimal promoter for a univector gene therapy approach based on its high tumor selectivity. Utilization of multiple epithelial cell-specific promoters may result in a more tissue-selective gene therapy approach. Using a combination of promoters may prevent potential problems due to expression in nonepithelial stem cells that may constitutively express hTERT.

Original languageEnglish (US)
Pages (from-to)451-458
Number of pages8
JournalGynecologic Oncology
Volume85
Issue number3
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Genetic Therapy
Ovarian Neoplasms
Genes
Luciferases
Neoplasms
Epithelial Cells
Polyomavirus Transforming Antigens
Cell Line
Organ Specificity
Tumor Cell Line
Transfection
Stem Cells
Epithelium
Carcinoma

Keywords

  • Ovarian cancer
  • Promoter
  • Tissue-specific
  • Tumor-specific

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Tanyi, J. L., Lapushin, R., Eder, A., Auersperg, N., Tabassam, F. H., Roth, J. A., ... Wolf, J. (2002). Identification of tissue- and cancer-selective promoters for the introduction of genes into human ovarian cancer cells. Gynecologic Oncology, 85(3), 451-458. https://doi.org/10.1006/gyno.2002.6644

Identification of tissue- and cancer-selective promoters for the introduction of genes into human ovarian cancer cells. / Tanyi, Janos L.; Lapushin, Ruth; Eder, Astrid; Auersperg, Nelly; Tabassam, Fazal H.; Roth, Jack A.; Gu, Jian; Fang, Binglian; Mills, Gordon; Wolf, Judith.

In: Gynecologic Oncology, Vol. 85, No. 3, 01.01.2002, p. 451-458.

Research output: Contribution to journalArticle

Tanyi, JL, Lapushin, R, Eder, A, Auersperg, N, Tabassam, FH, Roth, JA, Gu, J, Fang, B, Mills, G & Wolf, J 2002, 'Identification of tissue- and cancer-selective promoters for the introduction of genes into human ovarian cancer cells', Gynecologic Oncology, vol. 85, no. 3, pp. 451-458. https://doi.org/10.1006/gyno.2002.6644
Tanyi, Janos L. ; Lapushin, Ruth ; Eder, Astrid ; Auersperg, Nelly ; Tabassam, Fazal H. ; Roth, Jack A. ; Gu, Jian ; Fang, Binglian ; Mills, Gordon ; Wolf, Judith. / Identification of tissue- and cancer-selective promoters for the introduction of genes into human ovarian cancer cells. In: Gynecologic Oncology. 2002 ; Vol. 85, No. 3. pp. 451-458.
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abstract = "Objective. One potential limitation of gene therapy for epithelial tumors is the lack of tissue or tumor specificity of treatment. Tumor-selective expression of gene therapies may avoid deleterious side effects and improve the efficacy of the treatment. The aim of this study was to evaluate the tissue and tumor specificity of four different potential gene therapy promoters, to determine their usefulness in tissue-specific gene therapy of epithelial ovarian carcinomas. Methods. Three potential epithelial cell-selective (hESE1, SLP1, OSP1) and one potential tumor-selective (hTERT) promoter were placed upstream of a luciferase construct to determine relative activity in a wide variety of normal and malignant cell lines. Transient transfection and luciferase assays were carried out in 12 epithelial ovarian (3 SV40 T antigen-transfected normal and 9 malignant) and 8 control cell lines. Results. Luciferase assays revealed that the hTERT promoter presented the highest tumor selectivity, hESE1 and SLP1 promoters showed strong epithelial cell selectivity (hESE1, 16/17; SLP1, 15/17), with the OSP1 (11/17) promoter exhibiting lower epithelial selectivity. Of the potential promoters for gene therapy, hTERT promoter exhibited the strongest transcriptional activity in most of the tumor cell lines. None of the promoters exhibited strict ovarian epithelium selectivity. Conclusion. The hTERT promoter may be an optimal promoter for a univector gene therapy approach based on its high tumor selectivity. Utilization of multiple epithelial cell-specific promoters may result in a more tissue-selective gene therapy approach. Using a combination of promoters may prevent potential problems due to expression in nonepithelial stem cells that may constitutively express hTERT.",
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