Quantitative proteomic analysis of ovarian cancer cells identified mitochondrial proteins associated with Paclitaxel resistance.
Quantitative proteomic analysis of ovarian cancer cells identified mitochondrial proteins associated with Paclitaxel resistance.
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DOI：
10.1002/prca.200900005
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发表时间：
2009-11
影响因子：
2
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Tian, Yuan;Tan, Aik-Choon;Sun, Xiaer;Olson, Matthew T.;Xie, Zhi;Jinawath, Natini;Chan, Daniel W.;Shih, Le-Ming;Zhang, Zhen;Zhang, Hui
紫杉醇作为抗有丝分裂药物被广泛应用于多种癌症的化疗中，作为卵巢癌的一线化疗方案，其疗效显著。然而，紫杉醇耐药的频繁发生限制了其在长期治疗中的作用。尽管有大量的临床和细胞证据表明紫杉醇耐药肿瘤，但导致紫杉醇耐药的分子机制尚不清楚。使用基因组方法，我们之前已经确定了BTB/POZ基因Nac1与卵巢癌紫杉醇耐药之间的关联。本实验采用了多种定量蛋白质组学方法来鉴定与紫杉醇抗性和Nac1功能相关的蛋白质变化。通过诱导显性阴性Nac1表达的SKOV-3卵巢浆液性癌细胞系，研究了功能性Nac1存在和缺失时紫杉醇治疗相关的变化。使用iTRAQ标记和质谱进行定量蛋白质组学分析。两种无标记的定量蛋白质组学方法：LC-MS和光谱计数，以提高蛋白质组学定量的置信度。通过至少一种定量蛋白质组学方法，共对1371个蛋白进行了定量。本研究确定了与紫杉醇和NAC1功能相关的候选蛋白。对紫杉醇抗性蛋白变化的Go分析显示，细胞成分富集与线粒体有关。此外，微管蛋白和线粒体蛋白是与紫杉醇治疗相关的主要细胞成分。这表明线粒体可能在紫杉醇抵抗中起作用。
Paclitaxel has been widely used as an anti-mitotic agent in chemotherapy for a variety of cancers and adds substantial efficacy as the first-line chemotherapeutic regimen for ovarian cancers. However, the frequent occurrence of paclitaxel resistance limits its function in long-term management. Despite abundant clinical and cellular demonstration of paclitaxel resistant tumors, the molecular mechanisms leading to paclitaxel resistance are poorly understood. Using genomic approaches, we have previously identified an association between a BTB/POZ gene, Nac1, and paclitaxel resistance in ovarian cancer. The experiments presented here have applied multiple quantitative proteomic methods to identify protein changes associated with paclitaxel resistance and Nac1 function. The SKOV-3 ovarian serous carcinoma cell line, which has inducible expression of dominant negative Nac1, was used to determine the paclitaxel treatment associated changes in the presence and absence of functional Nac1. Quantitative proteomic analyses were performed using iTRAQ labeling and mass spectrometry. Two label-free quantitative proteomic methods: LC-MS and spectral count were used to increase confidence of proteomic quantification. A total of 1371 proteins were quantified by at least one of the quantitative proteomic methods. Candidate proteins related to paclitaxel and NAC1 function were identified in this study. Go analysis of the protein changes identified upon paclitaxel resistance revealed that cell component enrichment related to mitochondria. Moreover, tubulin and mitochondrial proteins were the major cellular components with changes associated with paclitaxel treatment. This suggests that mitochondria may play a role in paclitaxel resistance.
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影响因子：
4.8
作者：
Carré, M;André, N;Braguer, D
通讯作者：
Braguer, D
影响因子：
7
作者：
Ross, PL;Huang, YLN;Pappin, DJ
通讯作者：
Pappin, DJ
DOI：
10.1097/pgp.0b013e318156c838
发表时间：
2008-04-01
影响因子：
2.4
作者：
Umezu, Tomokazu;Shibata, Kiyosumi;Kikkawa, Fumitaka
通讯作者：
Kikkawa, Fumitaka
影响因子：
3.3
作者：
Sangrajrang, S;Fellous, A
通讯作者：
Fellous, A
影响因子：
7.4
作者：
Liu, HB;Sadygov, RG;Yates, JR
通讯作者：
Yates, JR