Tau expression in model adenocarcinomas correlates with docetaxel sensitivity in tumour-bearing mice.
Docetaxel is a new taxoid with clinical activity in breast and lung cancer. Using docetaxel-sensitive and -refractory mammary and pancreatic murine tumours, as well as human-derived neoplasms, we investigated if a determinant of docetaxel sensitivity could be found at the level of its mechanism of action. Because microtubules represent the cellular targets of the drug, we studied their heterogeneity in the tumour models to try to explain the differences in drug sensitivity. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the expression of microtubular components showed that levels of Mbeta4-tubulin and Tau mRNAs were higher in the murine sensitive neoplasms than in the refractory ones. It was also found that Tau protein levels differed markedly among the tumours. In the human-derived sensitive neoplasm, beta-tubulins and some Tau isoforms were found to be more abundant than in the resistant one. Western blot analysis of MAP2 revealed the presence of several immunoreactive species. Some of these polypeptides were also found in higher amounts in the docetaxel-sensitive tumours. The possible meaning of these correlations is discussed in connection with the regulation of microtubule dynamics.
Unité d'Immunogénétique Humaine, Institut Pasteur, Paris, France.
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Veitia
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MC
Bissery
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C
Martinez
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Fellous
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D043823:Taxoids; D014404:Tubulin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D043823:Taxoids; D014404:Tubulin; D016875:tau Proteins; D000077143:Docetaxel; D017239:Paclitaxel