Alterations of the WNT7A Gene in Clear Cell Renal Cell Carcinomas
| Autor: | Vladimir I. Kashuba, Y. M. Zgonnyk, Liubov A. Stoliar, Eugene R. Zabarovsky, V. V. Gordiyuk, Alina Romanenko, Aleksandr G. Kondratov, Alla Rynditch, Elena Kashuba, Sergiy M. Kvasha |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Tumor Physiology Loss of Heterozygosity lcsh:Medicine Epigenesis Genetic Loss of heterozygosity Teknik och teknologier Molecular Cell Biology Basic Cancer Research lcsh:Science Multidisciplinary Wnt signaling pathway Middle Aged Oncology Renal Cancer DNA methylation Azacitidine Medicine Engineering and Technology Epigenetics Female DNA modification Research Article Adult Genetic Markers Tumor suppressor gene Urology Down-Regulation WNT7A Gene Biology Decitabine Molecular Genetics Young Adult Cell Line Tumor Genetics Humans Gene silencing Carcinoma Renal Cell Aged Cell Proliferation Cell growth lcsh:R Renal Cell Carcinoma Cancers and Neoplasms DNA Methylation Molecular biology Wnt Proteins Genitourinary Tract Tumors lcsh:Q Gene expression Clear cell Microsatellite Repeats |
| Zdroj: | PLoS ONE, Vol 7, Iss 10, p e47012 (2012) PLoS ONE |
| Popis: | WNT7A (wingless-type MMTV integration site family, member 7A) is a known tumor suppressor gene of non-small cell lung carcinomas (NSCLC) and is frequently inactivated due to CpG-island hypermethylation in human cancers. The members of WNT family are involved in cell signaling and play crucial roles in cancer development. In the present work hypermethylation of the WNT7A gene was detected in 66% (29/44) of analyzed clear cell renal cell carcinomas (RCCs) using methyl-specific PCR (MSP). Moreover, bisulfite sequencing confirmed intensive hypermethylation of the 5-CpG island of the WNT7A gene. Methylation analysis revealed positive correlations between tumor stage, Fuhrman nuclear grade and WNT7A hypermethylation. Additionally, restoration of WNT7A gene expression in the A498 cell line by 5-aza-2-deoxycytidine treatment confirmed a direct contribution of hypermethylation in silencing of the WNT7A gene. High frequency of loss of heterozygosity (LOH) was demonstrated on chromosome 3p25 in regions surrounding the WNT7A gene. The frequent down-regulation of WNT7A gene expression was detected in 88% (15/17) of clear cell RCCs. We have also shown that the WNT7A gene possesses tumor suppression function by colony-formation and cell proliferation assays in RCC cell lines. In summary, the WNT7A gene is inactivated by genetic/epigenetic alterations in clear cell RCC and demonstrates tumor suppressor properties. Funding Agencies|State Fond of Fundamental Research|F46/457-2011|Swedish Cancer Society||Swedish Institute||Swedish Research Council||EACR |
| Databáze: | OpenAIRE |
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