OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation.
Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common in multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-08-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2500176?pdf=render |
| _version_ | 1819031921911398400 |
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| author | Yan Cui Ying Ying Andrew van Hasselt Ka Man Ng Jun Yu Qian Zhang Jie Jin Dingxie Liu Johng S Rhim Sun Young Rha Myriam Loyo Anthony T C Chan Gopesh Srivastava George S W Tsao Grant C Sellar Joseph J Y Sung David Sidransky Qian Tao |
| author_facet | Yan Cui Ying Ying Andrew van Hasselt Ka Man Ng Jun Yu Qian Zhang Jie Jin Dingxie Liu Johng S Rhim Sun Young Rha Myriam Loyo Anthony T C Chan Gopesh Srivastava George S W Tsao Grant C Sellar Joseph J Y Sung David Sidransky Qian Tao |
| author_sort | Yan Cui |
| collection | DOAJ |
| description | Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common in multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction.Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells with endogenous silencing.Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies. |
| first_indexed | 2024-12-21T06:53:44Z |
| format | Article |
| id | doaj.art-5fc2dd17e04e4aad8cfdd1e331172085 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T06:53:44Z |
| publishDate | 2008-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5fc2dd17e04e4aad8cfdd1e3311720852022-12-21T19:12:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-08-0138e299010.1371/journal.pone.0002990OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation.Yan CuiYing YingAndrew van HasseltKa Man NgJun YuQian ZhangJie JinDingxie LiuJohng S RhimSun Young RhaMyriam LoyoAnthony T C ChanGopesh SrivastavaGeorge S W TsaoGrant C SellarJoseph J Y SungDavid SidranskyQian TaoIdentification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common in multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction.Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells with endogenous silencing.Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies.http://europepmc.org/articles/PMC2500176?pdf=render |
| spellingShingle | Yan Cui Ying Ying Andrew van Hasselt Ka Man Ng Jun Yu Qian Zhang Jie Jin Dingxie Liu Johng S Rhim Sun Young Rha Myriam Loyo Anthony T C Chan Gopesh Srivastava George S W Tsao Grant C Sellar Joseph J Y Sung David Sidransky Qian Tao OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. PLoS ONE |
| title | OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. |
| title_full | OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. |
| title_fullStr | OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. |
| title_full_unstemmed | OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. |
| title_short | OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. |
| title_sort | opcml is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation |
| url | http://europepmc.org/articles/PMC2500176?pdf=render |
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