Faria Paula Cristina, Saba Karla, Neves Adriana Freitas, Cordeiro Elisangela Rosa, Marangoni Karina, Freitas Danielo Garcia, Goulart Luiz Ricardo
Federal University of Uberlândia, Institute of Genetics and Biochemistry, Molecular Genetics Laboratory, Uberlândia, MG, Brazil.
Cancer Invest. 2007 Dec;25(8):726-32. doi: 10.1080/07357900701600921.
The transforming growth factor beta 1 (TGF-beta1) is a multifunctional cytokine with several regulatory activities in tumor cells affecting growth, differentiation, and function. Alterations in gene expression, secretion, and regulation of TGF-beta1 may lead to a favorable environment for tumor development by angiogenesis stimulation and immune system suppression. We evaluated the influence of the TGFB1 polymorphisms by ARMS-PCR, Leu10Pro, and Arg25Pro, on prostate cancer (PCa) and benign prostatic hyperplasia (BPH). We assessed TGFB1 polymorphisms and their relation to mRNA levels (semi-quantitative RT-PCR) in blood samples as well as the implications in disease occurrence and progression. Peripheral blood samples from 175 patients were analyzed as to 92 BPH and 83 PCa. Samples obtained from 132 healthy males were used as negative controls. PCa patients with a Gleason score greater than 7 presented a higher frequency of the C allele (Leu10Pro). This allele was associated with a higher risk of developing PCa and BPH compared to the population (2.6 and 3.6 times higher, respectively). Patients with TGFB1 transcript levels equal to or more than 70% higher than control levels presented a 5.34 and 2.14-fold higher risk of having PCa and BPH, respectively, relative to the population. No association was detected between polymorphisms and mRNA levels. The C allele of the Leu10Pro polymorphism may predispose men to a more rapid cancer progression. Additionally, higher mRNA levels in the peripheral blood of PCa patients suggest that tumor cells may be disseminated in the circulation and could be used as a biomarker for extra-capsular invasion.
转化生长因子β1(TGF-β1)是一种多功能细胞因子,在肿瘤细胞中具有多种调节活性,影响生长、分化和功能。TGF-β1基因表达、分泌及调控的改变可能通过刺激血管生成和抑制免疫系统,为肿瘤发展创造有利环境。我们通过扩增阻滞突变系统聚合酶链反应(ARMS-PCR)评估了TGFB1基因Leu10Pro和Arg25Pro多态性对前列腺癌(PCa)和良性前列腺增生(BPH)的影响。我们评估了血液样本中TGFB1多态性及其与mRNA水平(半定量逆转录聚合酶链反应)的关系,以及它们在疾病发生和进展中的意义。分析了175例患者的外周血样本,其中92例为BPH患者,83例为PCa患者。从132名健康男性获取的样本用作阴性对照。Gleason评分大于7的PCa患者中,C等位基因(Leu10Pro)的频率更高。与总体人群相比,该等位基因与发生PCa和BPH的风险更高相关(分别高出2.6倍和3.6倍)。TGFB1转录水平等于或高于对照水平70%的患者,发生PCa和BPH的风险相对于总体人群分别高出5.34倍和2.1 .4倍。未检测到多态性与mRNA水平之间存在关联。Leu10Pro多态性的C等位基因可能使男性更容易出现癌症快速进展。此外,PCa患者外周血中较高的mRNA水平表明肿瘤细胞可能已播散至循环系统,可作为包膜外侵犯的生物标志物。