Nakazato T, Kanuma T, Tamura T, Faried L S, Aoki H, Minegishi T
Department of Gynecology and Reproductive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Int J Gynecol Cancer. 2007 Mar-Apr;17(2):426-32. doi: 10.1111/j.1525-1438.2007.00815.x. Epub 2007 Feb 2.
Clear cell adenocarcinoma of the ovary has a poor prognosis due to chemoresistance and early metastasis to the lymph nodes. It also can result in endometriosis and is the second most frequent type of ovarian cancer in Japan. Serous adenocarcinoma of the ovary is another common epithelial cancer tissue subtype in Japan, and it is highly sensitive to chemotherapy. In the current study, we examined the differential expression of genes in these types of ovarian cancer and tried to analyze their functions, especially as they relate to chemoresistance. We used differential display to compare clear cell carcinoma and serous adenocarcinoma of the ovary. We identified sperm protein 17 (SP17) as a candidate gene related to the chemoresistance of clear cell carcinoma. Its differential expression was confirmed by real-time polymerase chain reaction. Because the function of the SP17 gene in ovarian cancer is not known, we examined the effect of small interfering RNA targeting the SP17 gene on the chemoresistance and proliferation of ES-2 ovarian cancer cells to paclitaxel, currently the most effective treatment for ovarian cancer. We found that this treatment decreased the chemoresistance of these cells to paclitaxel. Our results strongly suggest that SP17 plays a role in the resistance of clear cell carcinoma to chemotherapy without influencing their ability to proliferate.
卵巢透明细胞腺癌预后较差,原因在于其具有化疗耐药性且早期易转移至淋巴结。它还可导致子宫内膜异位症,在日本是第二常见的卵巢癌类型。卵巢浆液性腺癌是日本另一种常见的上皮癌组织亚型,对化疗高度敏感。在本研究中,我们检测了这些类型卵巢癌中基因的差异表达,并试图分析它们的功能,尤其是与化疗耐药性相关的功能。我们采用差异显示技术比较卵巢透明细胞癌和浆液性腺癌。我们鉴定出精子蛋白17(SP17)为与透明细胞癌化疗耐药性相关的候选基因。通过实时聚合酶链反应证实了其差异表达。由于SP17基因在卵巢癌中的功能尚不清楚,我们检测了靶向SP17基因的小干扰RNA对ES - 2卵巢癌细胞对紫杉醇(目前治疗卵巢癌最有效的药物)的化疗耐药性和增殖的影响。我们发现这种处理降低了这些细胞对紫杉醇的化疗耐药性。我们的结果强烈表明,SP17在透明细胞癌对化疗的耐药性中起作用,而不影响其增殖能力。