Papanastasiou Anastasios D, Pampalakis Georgios, Katsaros Dionyssios, Sotiropoulou Georgia
Department of Pharmacy, School of Health Sciences, University of Patras, Rion-Patras, 26500, Greece.
Oncotarget. 2011 May;2(5):363-7. doi: 10.18632/oncotarget.258.
Netrin-1 (NTN1) is functionally important for the development of the nervous system.Interestingly, few recent studies showed that NTN1 may also promote cancer by increasing survival and resistance of lung and breast cancer cells to apoptosis. Our purpose was to investigate whether NTN1 and its receptor DCC may be involved in ovarian cancer. The NTN1 and DCC mRNAs were quantified by real-time RTPCR in normal (10), benign (8) and cancer (17) ovarian tissues. ALAS1 and TBP housekeeping genes were used for normalization. NTN1 was found overexpressed in 76% of ovarian cancer specimens (13/17) as compared to normal (0/10, p<0.004)and benign (1/8, p<0.008) samples. Increased NTN1 mRNA levels correlated with advanced tumor stage (stage III, n=8, 100%) and grade (grade 3, n=7, 100%). In contrast, DCC was found downregulated in 59% (10/17) of ovarian tumors tested but correlation was not significant when compared to normal or benign specimens. Here,we demonstrated that NTN1 may be involved in ovarian cancer as the expression of NTN1 mRNA is strongly upregulated in ovarian malignant tumors but not in benign tumors. The fact that increased NTN1 is specifically observed in cancerous tissues indicates that NTN1 may represent a novel candidate biomarker for ovarian cancer.
Netrin-1（NTN1）对神经系统的发育具有重要功能。有趣的是，最近的一些研究表明，NTN1还可能通过提高肺癌和乳腺癌细胞的存活率及抗凋亡能力来促进癌症发展。我们的目的是研究NTN1及其受体DCC是否参与卵巢癌的发生。通过实时逆转录聚合酶链反应（RT-PCR）对10例正常卵巢组织、8例良性卵巢组织和17例癌性卵巢组织中的NTN1和DCC信使核糖核酸（mRNA）进行定量分析。以δ-氨基-γ-酮戊酸合成酶1（ALAS1）和TATA盒结合蛋白（TBP）看家基因作为内参进行标准化。结果发现，与正常卵巢组织（0/10，p<0.004）和良性卵巢组织（1/8，p<0.008）相比，76%（13/17）的卵巢癌标本中NTN1呈过表达。NTN1 mRNA水平升高与肿瘤晚期（Ⅲ期，n = 8，100%）和高分级（3级，n = 7，100%）相关。相反，在所检测的17例卵巢肿瘤中，59%（10/17）的肿瘤DCC表达下调，但与正常或良性标本相比，相关性不显著。在此，我们证明NTN1可能参与卵巢癌的发生，因为NTN1 mRNA在卵巢恶性肿瘤中强烈上调，而在良性肿瘤中则无此现象。在癌组织中特异性观察到NTN1升高这一事实表明，NTN1可能是一种新型的卵巢癌候选生物标志物。
