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Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour‐suppressor transgenes
Author(s) -
Hellwinkel Olaf J. C.,
Müller Jürgen,
Pollmann Annika,
Kabisch Hartmut
Publication year - 2005
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.684
Subject(s) - transgene , transduction (biophysics) , biology , cell culture , tumor suppressor gene , retinoblastoma , cell growth , cancer research , wild type , cell cycle , retinoblastoma protein , cell , gene , suppressor , microbiology and biotechnology , carcinogenesis , genetics , mutant , biochemistry
Background One of the most widely studied gene therapeutic strategies for cancer is the introduction of tumour‐suppressor genes—generally p53—into the target cells. As the genes of p53 and/or retinoblastoma (Rb) are mutated in the major part of osteosarcomas (OS), we aimed to study the effect of p53 and Rb transgenes on a panel of five different osteosarcoma cell lines. Methods OS cell lines were transduced by adenoviral vectors delivering the transcription units of the wildtype p53 and the Rb gene. Effects of the transgenes alone and at additional cytostatic stress were studied by proliferation, alive/dead and cell cycle assays. Results The individual cells lines displayed divergent reactions to p53‐ or Rb‐transgene delivery reaching from cell death (SaOs‐2, U2OS at p53 transduction) over stopped or lowered cell division (MG‐63, K‐HOS, SJSA‐1 at p53 and Rb transduction) to nearly unhindered cell growth (U2OS at Rb transduction). In those OS cell lines reacting with lowered cell division to p53 or Rb delivery, cytostatics only moderately intensified the transgene effects. Surprisingly, these reactions were apparently not dependent on the functional status of the cellular p53 and/or Rb genes or on differences in the infectability of the cell lines by the adenoviral vectors. Most interestingly, the respective effects of the p53 or Rb transgenes were not multiplied by simultaneous transduction of both tumour‐suppressor genes. Conclusions The application of wildtype tumour‐suppressor gene therapy on genetically variable osteosarcomas may be efficient only in yet not identified genetic subgroups of this tumour entity. Hyperactive tumour‐suppressor transgenes could be an alternative. Copyright © 2004 John Wiley & Sons, Ltd.