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Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells

机译：紫杉醇耐药性卵巢癌细胞中stathmin水平和调控的改变

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Two paclitaxel(Ptx)-resistant ovarian cancer cell lines, 1A9/Ptx-10 and 1A9/Ptx-22, isolated from the 1A9 cell line (a clone of the A2780 line) by continuous exposure to Ptx and verapamil, have point mutations in their major -tubulin gene and in one or both alleles of their TP53 gene. These cells were examined for alterations in cell cycle regulators and the tubulin-binding protein stathmin. Unlike parental cells, neither 1A9/Ptx-10 nor 1A9/Ptx-22 expressed detectable levels of p21WAF1/Cip1, a putative transcriptional regulator of stathmin, but did overexpress stathmin and Bcl2. No differences were noted in the expression levels of proliferative cell nuclear antigen or tyrosine-phosphorylated p34Cdc2. Ptx treatment altered little the expression of stathmin in the parental cell line, although it increased p21WAF1/Cip1 levels several-fold. Infection of Ptx-resistant lines with a wild-type TP53-bearing adenovirus (AdWTp53) changed cell cycle distribution and increased the levels of p21WAF1/Cip1, but caused no changes in stathmin levels. Microtubule drug resistance in ovarian carcinoma may be associated with altered p53/21WAF1/Cip1 regulatory pathways for stathmin expression and function.
机译：通过持续暴露于Ptx和维拉帕米而从1A9细胞系（A2780系的一个克隆）中分离出的两个耐紫杉醇（Ptx）的卵巢癌细胞系1A9 / Ptx-10和1A9 / Ptx-22在它们的主要微管蛋白基因以及它们的TP53基因的一个或两个等位基因中。检查这些细胞中细胞周期调节剂和微管蛋白结合蛋白stathmin的改变。与亲代细胞不同，1A9 / Ptx-10和1A9 / Ptx-22均未检测到p21WAF1 / Cip1的可检测水平，p21WAF1 / Cip1是stathmin的假定转录调节因子，但确实过表达stathmin和Bcl2。增殖细胞核抗原或酪氨酸磷酸化的p34Cdc2的表达水平未见差异。尽管Ptx处理将p21WAF1 / Cip1水平提高了几倍，但其对亲代细胞系中stathmin表达的影响很小。用带有野生型TP53的腺病毒（AdWTp53）感染耐Ptx的品系可以改变细胞周期分布并增加p21WAF1 / Cip1的水平，但不会导致Stathmin水平的变化。卵巢癌中的微管耐药性可能与改变的p53 / 21WAF1 / Cip1调节途径有关，使其表达和功能有关。

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