Altered expression pattern of topoisomerase IIα in ovarian tumor epithelial and stromal cells after platinum-based chemotherapy
Altered expression pattern of topoisomerase IIα in ovarian tumor epithelial and stromal cells after platinum-based chemotherapy
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DOI：
10.1593/neo.05580
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Dahl, Edgar
中科院分区：
文献类型：
--
作者：
Chekerov, Radoslav;Klaman, Irina;Dahl, Edgar
目的：探讨拓扑异构酶Ⅱ α（Topoisomerase II alpha，TOP 2A）在卵巢癌上皮细胞和间质细胞中的表达。方法：采用正交设计法使用定量真实的RT-PCR（n = 38）、RNA原位杂交（n = 13）和免疫组织化学（n = 69）分析正常卵巢组织和激光显微切割的卵巢肿瘤上皮细胞和邻近基质细胞中的TOP 2A表达。结果如下：TOP 2A mRNA通过RNA原位杂交在所有卵巢癌样品中检测到，与相邻基质细胞相比，肿瘤上皮细胞中的杂交信号更强。免疫组化发现相同的表达模式（P = .0001）。非常有趣的是，在铂类化疗后复发性卵巢癌中发现了TOP 2A的特异性变化：与原发性卵巢癌相比，复发性卵巢癌的肿瘤上皮细胞中TOP 2A表达降低（P = .056），而肿瘤相邻基质细胞中TOP 2A表达增加（P = .023）。结论：卵巢癌中TOP 2A mRNA和蛋白表达在肿瘤上皮细胞和邻近基质细胞中表现出特异性模式，其在基于铂的化疗后受到差异调节。这些数据支持间质区室在肿瘤进展中的可能重要性，并表明肿瘤间质细胞可能与卵巢癌化疗耐药性的发展有关。
OBJECTIVE: The aim of this study was to evaluate the expression of topoisomerase II alpha (TOP2A) in epithelial and stromal cells of ovarian cancer. METHODS: TOP2A expression was analyzed in normal ovarian tissue and in laser-microdissected ovarian tumor epithelial and adjacent stromal cells using quantitative real time RT-PCR (n = 38), RNA in situ hybridization (n = 13), and immunhistochemistry (n = 69). Results: TOP2A mRNA was detected by RNA in situ hybridization in all ovarian cancer samples, with stronger hybridization signals in tumor epithelial cells compared to adjacent stromal cells. The same expression pattern was found by immunohistochemistry (P = .0001). Very interestingly, specific changes of TOP2A were found in recurrent ovarian cancer after platinum-based chemotherapy: TOP2A expression decreased in tumor epithelial cells (P = .056) of recurrent ovarian cancer, whereas it increased in tumor adjacent stromal cells (P = .023) compared to primary ovarian cancer. CONCLUSION: TOP2A mRNA and protein expressions in ovarian cancer exhibit specific patterns in tumor epithelial and adjacent stromal cells, which are differentially modulated after platinum-based chemotherapy. These data support the possible importance of the stromal compartment in tumor progression and suggest that tumor stromal cells might be relevant to the development of chemotherapy resistance in ovarian cancer.