Laudański Piotr, Kowalczuk Oksana, Klasa-Mazurkiewicz Dagmara, Milczek Tomasz, Rysak-Luberowicz Dominik, Garbowicz Magdalena, Baranowski Włodzimierz, Charkiewicz Radosław, Szamatowicz Jacek, Chyczewski Lech
Department of Perinatology, Medical University of Bialystok, Poland.
Folia Histochem Cytobiol. 2011;49(2):317-24. doi: 10.5603/fhc.2011.0044.
The aim of this study was to selectively profile the activation status of mammalian target of rapamycin (mTOR)-associated oncogenes and tumor suppressor genes (TSGs) in ovarian cancer specimens, healthy ovaries and benign ovarian tumors, including endometrial cysts. We used a novel type of microfluidic gene array to examine the expression of 15 human tumor suppressors and oncogenes in ovarian cancer specimens of 53 patients, benign ovarian cysts of 29 women (endometrial and simple) and 11 healthy ovaries of individuals in whom the material was obtained during total hysterectomies performed because of fibroid changes. The array was custom-designed to include the following genes: NF1, RHEB, mTOR1, AKT-1, PTEN, TSC1, TSC2, KRAS, RPS6KB1, 4EBP1, TP53, EIF4E, STK11, PIK3CA and BECN1. Confirmatory immunohistochemical detection was performed for a group of selected proteins. Particularly significant differences were observed as to the expression of PTEN (p < 0.0001), TP53 (p = 0.0003), PIK3CA (p = 0.0003) and BECN1 (p = 0.0014) which were shown to be downregulated in cancer patients when compared to healthy ovaries and benign ovarian cysts (endometrial and simple). These markers did not show association with grade or stage of the tumor. Immunohistochemistry showed that PTEN, TP53, PIK3CA and BECN1 proteins are expressed in ovarian cancer. Our results indicate that there are significant differences in the expression of some of the mTOR-related tumor suppressors and oncogenes which could be associated with the pathogenesis of ovarian cancer.
本研究的目的是选择性地分析雷帕霉素哺乳动物靶点（mTOR）相关癌基因和肿瘤抑制基因（TSG）在卵巢癌标本、健康卵巢及良性卵巢肿瘤（包括子宫内膜囊肿）中的激活状态。我们使用一种新型微流控基因芯片检测了53例卵巢癌患者的标本、29名女性（子宫内膜囊肿和单纯囊肿）的良性卵巢囊肿以及11例因肌瘤病变在全子宫切除术中获取材料的个体的健康卵巢中15种人类肿瘤抑制基因和癌基因的表达。该芯片经定制设计，包含以下基因：NF1、RHEB、mTOR1、AKT - 1、PTEN、TSC1、TSC2、KRAS、RPS6KB1、4EBP1、TP53、EIF4E、STK11、PIK3CA和BECN1。对一组选定的蛋白质进行了验证性免疫组化检测。结果观察到，与健康卵巢和良性卵巢囊肿（子宫内膜囊肿和单纯囊肿）相比，PTEN（p < 0.0001）、TP53（p = 0.0003）、PIK3CA（p = 0.0003）和BECN1（p = 0.0014）的表达存在显著差异，这些基因在癌症患者中呈下调状态。这些标志物与肿瘤的分级或分期无关。免疫组化显示，PTEN、TP53、PIK3CA和BECN1蛋白在卵巢癌中表达。我们的结果表明，一些与mTOR相关的肿瘤抑制基因和癌基因的表达存在显著差异，这可能与卵巢癌的发病机制有关。
