Veitia R, Bissery M C, Martinez C, Fellous A
Unité d'Immunogénétique Humaine, Institut Pasteur, Paris, France.
Br J Cancer. 1998 Oct;78(7):871-7. doi: 10.1038/bjc.1998.595.
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.
多西他赛是一种对乳腺癌和肺癌具有临床活性的新型紫杉烷类药物。我们使用对多西他赛敏感和耐药的乳腺及胰腺小鼠肿瘤以及人源肿瘤，研究是否能在其作用机制层面找到多西他赛敏感性的决定因素。由于微管是该药物的细胞靶点，我们研究了它们在肿瘤模型中的异质性，试图解释药物敏感性的差异。对微管成分表达进行逆转录聚合酶链反应（RT-PCR）分析表明，小鼠敏感肿瘤中Mbeta4-微管蛋白和Tau mRNA的水平高于耐药肿瘤。还发现肿瘤之间Tau蛋白水平差异显著。在人源敏感肿瘤中，β-微管蛋白和一些Tau异构体比耐药肿瘤中更为丰富。对微管相关蛋白2（MAP2）的蛋白质免疫印迹分析显示存在几种免疫反应性条带。其中一些多肽在多西他赛敏感肿瘤中的含量也更高。结合微管动力学的调节对这些相关性的可能意义进行了讨论。
