Adenoviraler Transfer von bax unter der Kontrolle des CEA Promotors induziert Apoptose in Kolonkarzinomzellen in vitro und in vivo

  • A. Beham
  • M. Vogel
  • M. Rentsch
  • T. Dobner
  • T. J. McDonnell
  • A. Fürst
  • E. K. Geissler
  • K. W. Jauch
Conference paper
Part of the Deutsche Gesellschaft für Chirurgie book series (DTGESCHIR, volume 31)

Abstract

Genetic alterations in apoptotic pathways impair the ability of cancer cells to undergo programmed cell death compared to normal tissue. Development of a cancer treatment strategy that specifically targets neoplastic cells, and that triggers downstream apoptotic pathways insensitive to alteration, could be optimally effective. To test the feasibility of this approach we put the proapototic bcl-2 family member bax under control of a promoter from the CEA gene that is frequently expressed by colon cancer cells. More specifically, we engineered an adenoviral construct, which places the fragment from – 244 to – 1 of the CEA promoter in front of the bax cDNA. After cloning the CEA promoter-bax in the pAdTrack vector, recombination and virus amplification was performed. Results showed by western blot and immunohistochemical analysis that virally infected CEA positive LoVo, HT29 and DLD1 cells expressed elevated bax protein levels after 24, 36 and 56 h, while CEA negative 293 or HepG2 control cells showed no enhancement of bax expression. Furthermore the higher bax expression in LoVo cells was associated with increased cell death, as demonstrated by flow cytometry after propidium iodide staining in vitro. In vivo treatment of LoVo liver metastases showed specific bax expression compared to normal liver after viral infection. Additional bax expression in LoVoliver metastases was associated with positive TUNEL staining. In conclusion, our data suggest that induction of programmed cell death by overexpression of bax, under the control of the CEA promoter, could be a useful therapeutic approach for colon cancer therapy.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • A. Beham
    • 1
    • 4
  • M. Vogel
    • 1
  • M. Rentsch
    • 1
  • T. Dobner
    • 2
  • T. J. McDonnell
    • 3
  • A. Fürst
    • 1
  • E. K. Geissler
    • 1
  • K. W. Jauch
    • 1
  1. 1.Chirurgische Klinik und PoliklinikGermany
  2. 2.Mikrobiologisches InstitutUniversität RegensburgGermany
  3. 3.M. D. Anderson Cancer CenterHoustonUSA
  4. 4.Chirurgische Klinik und PoliklinikUniversität RegensburgRegensburgGermany

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