Cyclin A1 expression and paclitaxel resistance in human ovarian cancer cells.
Cyclin A1 expression and paclitaxel resistance in human ovarian cancer cells.
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人类卵巢癌细胞中的细胞周期蛋白A1表达和紫杉醇抗性。
DOI：
10.1016/j.ejca.2016.08.007
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发表时间：
2016-11
影响因子：
8.4
通讯作者：
Ng, Shu-Wing
中科院分区：
文献类型：
--
作者：
Huang, Kuan-Chun;Yang, Junzheng;Ng, Michelle C.;Ng, Shu-Kay;Welch, William R.;Muto, Michael G.;Berkowitz, Ross S.;Ng, Shu-Wing
对化疗药物的内在和获得性耐药性的发展是卵巢癌成功化疗的主要障碍。化学反应相关生物标志物的鉴定和表征对于新的治疗开发至关重要。通过高通量微阵列分析获得全局RNA表达谱。细胞周期，增殖率和紫杉醇敏感性的卵巢癌细胞周期蛋白A1诱导表达构建体进行了比较与四环素诱导，以及当细胞周期蛋白A1的表达被短抑制RNA（siRNA）抑制。β-半乳糖苷酶活性染色法检测细胞衰老。全球RNA表达谱和随后的基因表达水平和药物反应的相关性研究已经确定，细胞周期蛋白A1（CCNA 1）的表达升高与细胞对紫杉醇，阿霉素和5-氟尿嘧啶的耐药性显著相关。在卵巢癌细胞中证实了细胞周期蛋白A1在紫杉醇耐药性中的作用，该细胞具有诱导型细胞周期蛋白A1表达结构，当细胞周期蛋白A1表达被诱导时，该结构显示紫杉醇介导的生长抑制和凋亡减少，而在相同的细胞系中使用细胞周期蛋白A1特异性siRNA下调细胞周期蛋白A1表达使细胞对紫杉醇毒性敏感。而异位表达cyclin A1的卵巢癌细胞增殖和衰老相关的β-半乳糖苷酶活性下降。我们的分析和相关性研究已经确定细胞周期蛋白A1作为卵巢癌化疗耐药相关的生物标志物。表征研究的结果表明，细胞周期蛋白A1的功能作为一个癌基因，控制肿瘤发生和化疗耐药的增殖和生存活动。
The development of intrinsic and acquired resistance to antineoplastic agents is a major obstacle to successful chemotherapy in ovarian cancers. Identification and characterization of chemoresponse-associated biomarkers is of paramount importance for novel therapeutic development. Global RNA expression profiles were obtained by high-throughput microarray analysis. Cell cycle, proliferation rate, and paclitaxel sensitivity of ovarian cancer cells harboring cyclin A1 inducible expression construct was compared with and without tetracyclin induction, as well as when the cyclin A1 expression was suppressed by short inhibiting RNA (siRNA). Cellular senescence was evaluated by β-galactosidase activity staining. Global RNA expression profiling and subsequent correlation studies of gene expression level and drug response has identified that elevated expression of cyclin A1 (CCNA1) was significantly associated with cellular resistance to paclitaxel, doxorubicin and 5-fluorouracil. The role of cyclin A1 in paclitaxel resistance was confirmed in ovarian cancer cells that harbor an inducible cyclin A1 expression construct, which showed reduced paclitaxel-mediated growth inhibition and apoptosis when cyclin A1 expression was induced, whereas down-regulation of cyclin A1 expression in the same cell lines using cyclin A1-specific siRNAs sensitized the cells to paclitaxel toxicity. However, ovarian cancer cells with ectopic expression of cyclin A1 demonstrated slow down of proliferation and senescence-associated β-galactosidase activity. Our profiling and correlation studies have identified cyclin A1 as one chemoresistance-associated biomarker in ovarian cancer. The results of the characterization studies suggest that cyclin A1 functions as an oncogene that controls proliferative and survival activities in tumorigenesis and chemo-resistance of ovarian cancer.
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影响因子：
12.4
作者：
Lee, J-J;Kim, B. C.;Lee, J-S
通讯作者：
Lee, J-S
影响因子：
5.3
作者：
MELINO, G;ANNICCHIARICOPETRUZZELLI, M;PIACENTINI, M
通讯作者：
PIACENTINI, M
影响因子：
56.9
作者：
Huang, Haojie;Regan, Kevin M.;Tindall, Donald J.
通讯作者：
Tindall, Donald J.
DOI：
10.1073/pnas.92.10.4507
发表时间：
1995-05-09
影响因子：
11.1
作者：
HALDAR, S;JENA, N;CROCE, CM
通讯作者：
CROCE, CM
影响因子：
4.8
作者：
Jin, DY;Teramoto, H;Jeang, KT
通讯作者：
Jeang, KT