Nowakowska Magdalena, Pospiech Karolina, Lewandowska Urszula, Piastowska-Ciesielska Agnieszka W, Bednarek Andrzej Kazimierz
Department of Molecular Cancerogenesis, Medical University of Lodz, Zeligowskiego 7/9, 90-752, Lodz, Poland,
Tumour Biol. 2014 Sep;35(9):9291-301. doi: 10.1007/s13277-014-2196-2. Epub 2014 Jun 19.
WW-domain-containing oxidoreductase (WWOX) is the tumour suppressor gene from the common fragile site FRA16D, whose altered expression has been observed in tumours of various origins. Its suppressive role and influence on basic cellular processes such as proliferation and apoptosis have been confirmed in many in vitro and in vivo studies. Moreover, its protein is thought to take part in the regulation of tissue morphogenesis and cell differentiation. However, its role in colon cancer formation remains unclear. The aim of this study was to characterize the influence of WWOX on the process of colon cancerogenesis, the basic features of the cancer cell and its expression profiles. Multiple biological tests, microarray experiments and quantitative reverse transcriptase (RT)-PCR were performed on two colon cancer cell lines, HT29 and SW480, which differ in morphology, expression of differentiation markers, migratory characteristics and metastasis potential and which represent negative (HT29) and low (SW480) WWOX expression levels. The cell lines were subjected to retroviral transfection, inducting WWOX overexpression. WWOX was found to have diverse effects on proliferation, apoptosis and the adhesion potential of modified cell lines. Our observations suggest that in the HT29 colon cancer cell line, increased expression of WWOX may result in the transition of cancer cells into a more normal colon epithelium phenotype, while in SW480, WWOX demonstrated well-known tumour suppressor properties. Our results also suggest that WWOX does not behave as classical tumour suppressor gene, and its influence on cell functioning is more global and complicated.
含WW结构域的氧化还原酶（WWOX）是位于常见脆性位点FRA16D的肿瘤抑制基因，在各种起源的肿瘤中均观察到其表达改变。在许多体外和体内研究中已证实其对增殖和凋亡等基本细胞过程的抑制作用和影响。此外，其蛋白质被认为参与组织形态发生和细胞分化的调节。然而，其在结肠癌形成中的作用仍不清楚。本研究的目的是明确WWOX对结肠癌发生过程、癌细胞基本特征及其表达谱的影响。对两种结肠癌细胞系HT29和SW480进行了多项生物学测试、微阵列实验和定量逆转录酶（RT）-PCR，这两种细胞系在形态、分化标志物表达、迁移特性和转移潜能方面存在差异，分别代表WWOX表达水平为阴性（HT29）和低水平（SW480）。对这些细胞系进行逆转录病毒转染，诱导WWOX过表达。发现WWOX对修饰细胞系的增殖、凋亡和黏附潜能有多种影响。我们的观察结果表明，在HT29结肠癌细胞系中，WWOX表达增加可能导致癌细胞转变为更正常的结肠上皮表型，而在SW480中，WWOX表现出众所周知的肿瘤抑制特性。我们的结果还表明，WWOX的行为不同于经典的肿瘤抑制基因，其对细胞功能的影响更为全面和复杂。
