Differential gene expression in a paclitaxel-resistant clone of a head and neck cancer cell line.
The anti-neoplastic drug paclitaxel (taxol), which is known to block cells in the G2/M phase of the cell cycle through stabilization of microtubules, is meanwhile commonly used for chemotherapy of advanced head and neck cancer. Chemotherapy is primarily used in order to preserve laryngeal and/or pharyngeal structures. Although paclitaxel generally seems to be a powerful agent, it failed to reach a loco-regional tumor control in a sufficient percentage of patients. In order to investigate molecular resistance mechanisms, we have established a paclitaxel-resistant subline originating from the larynx carcinoma cell line HLaC79, which seemed to be partially dependent on taxol. The original and the descendant cell line were characterized by growth inhibition assays. We used western blotting and the cDNA subtraction (SSH) technique to identify genes differentially expressed in the taxol-resistant cell clone. cDNA subtraction revealed increased expression of six genes, including clathrin heavy chain, alpha3-tubulin, a neuroblastoma-specific Thymosin beta, the ribosomal protein L7a, HLA-B associated transcript 3 and collagen IIIalpha1 in the taxol-resistant cell line. Furthermore, western blots showed an overexpression of MDR-1 in the taxol-resistant clone, while alpha- and beta-tubulins and p48/IRF9 were expressed in equal amounts in both cell lines.
Schmidt
Marianne
M
Department of Otorhinolaryngology, University of Würzburg, Josef-Schneider-Strasse 11, 97080, Würzburg, Germany. marianne.schmidt@mail.uni-wuerzburg.de
Schler
Gabriele
G
Gruensfelder
Petra
P
Hoppe
Florian
F
D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000235:genetics*; D017239:Paclitaxel / Q000627:therapeutic use; D012334:RNA, Neoplasm / Q000235:genetics*; D014404:Tubulin / Q000235:genetics*; D050257:Tubulin Modulators / Q000627:therapeutic use
D014408:Biomarkers, Tumor; C494227:IRF9 protein, human; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D012334:RNA, Neoplasm; D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel