Media type: E-Article Title: Identification of drug‐regulated genes in osteosarcoma cells Contributor: Fellenberg, Jörg; Dechant, Markus J.; Ewerbeck, Volker; Mau, Hans Published: Wiley, 2003 Published in: International Journal of Cancer, 105 (2003) 5, Seite 636-643 Language: English DOI: 10.1002/ijc.11135 ISSN: 0020-7136; 1097-0215 Keywords: Cancer Research ; Oncology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>The introduction of systemic chemotherapy improved significantly the prognosis of osteosarcoma. Despite this success, approximately 30–40% of patients will relapse. Cytotoxic drugs have been shown to induce apoptosis in the target cells independent of their primary effects. The underlying molecular mechanisms and the intracellular mediators, however, are still largely unknown. Therefore, the purpose of our study was to identify drug‐regulated genes in osteosarcoma cells useful as prognostic factors and for the development of new therapeutic strategies. Using suppressive subtractive hybridization (SSH) the gene expression pattern of untreated Saos‐2 cells was compared to cells treated with cisplatin, methotrexate and doxorubicin, respectively. We identified 8 genes that are regulated >2‐fold in drug‐treated osteosarcoma cell lines. Expression of ferritin light chain, <jats:italic>rhoA</jats:italic>, ino<jats:italic>sine monophosphatdgehydrogenase II</jats:italic>, <jats:italic>ribonucleotide reductase M2</jats:italic>, <jats:italic>pro2000</jats:italic> and <jats:italic>pro1859</jats:italic> were increased after drug treatment, whereas <jats:italic>prohibitin</jats:italic> and α‐<jats:italic>actinin</jats:italic> expressions were significantly downregulated. Differential expression of the identified genes was verified by Northern blot analysis of 3 different osteosarcoma cell lines. In addition, the effects on chemosensitivity of 4 selected genes was analyzed by overexpression of recombinant constructs in Saos‐2 cells and subsequent quantification of drug‐induced apoptosis. Overexpression of <jats:italic>prohibitin</jats:italic> and <jats:italic>rhoA</jats:italic> reduced significantly drug sensitivity to approximately 52% and 59% indicating a crucial role in the modulation of drug‐induced cell death. © 2003 Wiley‐Liss, Inc.</jats:p> Access State: Open Access