The <it>14-3-3</it>σ gene promoter is methylated in both human melanocytes and melanoma
<p>Abstract</p> <p>Background</p> <p>Recent evidence demonstrates that 14-3-3σ acts as a tumor suppressor gene inactivated by methylation of its 5' CpG islands in epithelial tumor cells, while remaining un-methylated in normal human epithelia. The methylation analy...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-05-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/9/162 |
| _version_ | 1818834490454179840 |
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| author | Fodstad Oystein Howell Paul Ren Suping Liu Suhu Riker Adam I |
| author_facet | Fodstad Oystein Howell Paul Ren Suping Liu Suhu Riker Adam I |
| author_sort | Fodstad Oystein |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Recent evidence demonstrates that 14-3-3σ acts as a tumor suppressor gene inactivated by methylation of its 5' CpG islands in epithelial tumor cells, while remaining un-methylated in normal human epithelia. The methylation analysis of 14-3-3σ has been largely overlooked in melanoma.</p> <p>Methods</p> <p>The methylation status of 14-3-3σ CpG island in melanocytes and melanoma cells was analyzed by methylation-specific sequencing (MSS) and quantitative methylation-specific PCR (Q-MSP). 14-3-3σ mRNA and protein expression in cell lines was detected by real-time RT-PCR and western blot. Melanoma cells were also treated by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, and/or histone deacetylase inhibitor, Trichostatin A (TSA), to evaluate their effects on 14-3-3σ gene expression.</p> <p>Results</p> <p>14-3-3σ is hypermethylated in both human melanocytes and most melanoma cells in a lineage-specific manner, resulting in the silencing of 14-3-3σ gene expression and the active induction of 14-3-3σ mRNA and protein expression following treatment with DAC. We also observed a synergistic effect upon gene expression when DAC was combined with TSA. The promoter methylation status of 14-3-3σ was analyzed utilizing Q-MSP in 20 melanoma tissue samples and 10 cell lines derived from these samples, showing that the majority of melanoma samples maintain their hypermethylation status of the 14-3-3σ gene.</p> <p>Conclusion</p> <p>14-3-3σ is hypermethylated in human melanoma in a cell-linage specific manner. Spontaneous demethylation and re-expression of 14-3-3σ is a rare event in melanoma, indicating 14-3-3σ might have a tentative role in the pathogenesis of melanoma.</p> |
| first_indexed | 2024-12-19T02:35:39Z |
| format | Article |
| id | doaj.art-9bc5dbe786394af9ae017edbbfd54fef |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-19T02:35:39Z |
| publishDate | 2009-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-9bc5dbe786394af9ae017edbbfd54fef2022-12-21T20:39:26ZengBMCBMC Cancer1471-24072009-05-019116210.1186/1471-2407-9-162The <it>14-3-3</it>σ gene promoter is methylated in both human melanocytes and melanomaFodstad OysteinHowell PaulRen SupingLiu SuhuRiker Adam I<p>Abstract</p> <p>Background</p> <p>Recent evidence demonstrates that 14-3-3σ acts as a tumor suppressor gene inactivated by methylation of its 5' CpG islands in epithelial tumor cells, while remaining un-methylated in normal human epithelia. The methylation analysis of 14-3-3σ has been largely overlooked in melanoma.</p> <p>Methods</p> <p>The methylation status of 14-3-3σ CpG island in melanocytes and melanoma cells was analyzed by methylation-specific sequencing (MSS) and quantitative methylation-specific PCR (Q-MSP). 14-3-3σ mRNA and protein expression in cell lines was detected by real-time RT-PCR and western blot. Melanoma cells were also treated by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, and/or histone deacetylase inhibitor, Trichostatin A (TSA), to evaluate their effects on 14-3-3σ gene expression.</p> <p>Results</p> <p>14-3-3σ is hypermethylated in both human melanocytes and most melanoma cells in a lineage-specific manner, resulting in the silencing of 14-3-3σ gene expression and the active induction of 14-3-3σ mRNA and protein expression following treatment with DAC. We also observed a synergistic effect upon gene expression when DAC was combined with TSA. The promoter methylation status of 14-3-3σ was analyzed utilizing Q-MSP in 20 melanoma tissue samples and 10 cell lines derived from these samples, showing that the majority of melanoma samples maintain their hypermethylation status of the 14-3-3σ gene.</p> <p>Conclusion</p> <p>14-3-3σ is hypermethylated in human melanoma in a cell-linage specific manner. Spontaneous demethylation and re-expression of 14-3-3σ is a rare event in melanoma, indicating 14-3-3σ might have a tentative role in the pathogenesis of melanoma.</p>http://www.biomedcentral.com/1471-2407/9/162 |
| spellingShingle | Fodstad Oystein Howell Paul Ren Suping Liu Suhu Riker Adam I The <it>14-3-3</it>σ gene promoter is methylated in both human melanocytes and melanoma BMC Cancer |
| title | The <it>14-3-3</it>σ gene promoter is methylated in both human melanocytes and melanoma |
| title_full | The <it>14-3-3</it>σ gene promoter is methylated in both human melanocytes and melanoma |
| title_fullStr | The <it>14-3-3</it>σ gene promoter is methylated in both human melanocytes and melanoma |
| title_full_unstemmed | The <it>14-3-3</it>σ gene promoter is methylated in both human melanocytes and melanoma |
| title_short | The <it>14-3-3</it>σ gene promoter is methylated in both human melanocytes and melanoma |
| title_sort | it 14 3 3 it σ gene promoter is methylated in both human melanocytes and melanoma |
| url | http://www.biomedcentral.com/1471-2407/9/162 |
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