Gene therapy for endometrial carcinoma with the herpes simplex thymidine kinase gene Journal Article


Authors: Ugur Ural, A.; Takebe, N.; Adhikari, D.; Ercikan-Abali, E.; Banerjee, D.; Barakat, R.; Bertino, J. R.
Article Title: Gene therapy for endometrial carcinoma with the herpes simplex thymidine kinase gene
Abstract: We investigated whether retrovirus-mediated transfer of the herpes simplex thymidine kinase gene into a human endometrial carcinoma (EC4) cell line can sensitize these cells to the prodrug ganciclovir (GCV) and thereby provide a therapeutic option for this cancer. A retrovirus encoding for the herpes simplex virus tip-1 (HSV) thymidine kinase (tk) gene was generated in which expression of tk is under control of the myeloproliferative sarcoma virus (MPSV) promoter/enhancer. We used human mutated dihydrofolate reductase (DHFR) cDNA as a selectable marker. Expression of tk was confirmed by Northern blot analysis and reverse transcription polymerase chain reaction. We demonstrated that the combination of retrovirally mediated tk gene transfer and GCV treatment effectively inhibits proliferation and causes death of EC4 cells in vitro. A bystander killing effect was observed when 90% of uninfected tumor cells were mixed with only 10% of HSVtk- infected cells. We suggest that a gene therapy approach to endometrial carcinoma can be established using retroviral transfer of HSVtk to tumor cells and subsequent administration of GCV. (C) 2000 Academic Press.
Keywords: controlled study; human cell; nonhuman; endometrium carcinoma; endometrial neoplasms; animal cell; mouse; reverse transcription polymerase chain reaction; gene product; herpes simplex; drug screening assays, antitumor; tumor cells, cultured; genetic vectors; reverse transcriptase polymerase chain reaction; rna, messenger; gene therapy; thymidine kinase; dihydrofolate reductase; herpes simplex virus; endometrial carcinoma; ganciclovir; cell strain 3t3; complementary dna; retrovirus; retroviridae; antiviral agents; northern blotting; gene transfer techniques; prodrugs; virus enzyme; genes, viral; humans; human; female; priority journal; article
Journal Title: Gynecologic Oncology
Volume: 76
Issue: 3
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2000-03-01
Start Page: 305
End Page: 310
Language: English
DOI: 10.1006/gyno.1999.5707
PUBMED: 10684701
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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Citation Impact
MSK Authors
  1. Debabrata Banerjee
    136 Banerjee
  2. Richard R Barakat
    629 Barakat
  3. Naoko Takebe
    25 Takebe
  4. Joseph Bertino
    363 Bertino
  5. Emine A Ercikan
    23 Ercikan