Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-014-2196-2) contains supplementary material, which is available to authorized users.
Highlights
Colorectal cancer (CRC) is one of the most common cancers in Western countries
Increased WWOX messenger RNA (mRNA) and protein expression was identified in both colon cancer cell lines (Figs. 1 and 2; Tables 1 and 2)
In SW480, the fold change in WWOX mRNA expression between transfection variants was more than 137 times, in HT29 more than 37 times
Summary
Colorectal cancer (CRC) is one of the most common cancers in Western countries. According to American Cancer Society in 2013, it will account for 9 % of new cancer cases and 9 % of tumour-associated deaths, independently on gender [1]. The majority of CRC cases are sporadic, and three distinct developmental molecular pathways have been described, based on molecular changes within colon epithelial cells. The second pathway, microsatellite instability (MSI), is expressed as frameshift mutations within short, tandemly repeated nucleotide sequences which arise as a consequence of disorders in the DNA mismatch repair system.
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