Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal Carcinoma
Aberrant retinoid signaling in human cancers is extending from the nucleus to the cytoplasm. Recently, we have demonstrated frequent epigenetic inactivation of a retinoic acid receptor (RAR), RARβ2, in nasopharyngeal carcinoma (NPC). To further explore targets contributing to aberrant retinoid signa...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558605801009 |
| _version_ | 1819058755309928448 |
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| author | Joseph Kwong Kwok-Wai Lo Lillian Shuk-Nga Chow Ka-Fai To Kwong-Wai Choy Franky Leung Chan Samuel C. Mok Dolly P. Huang |
| author_facet | Joseph Kwong Kwok-Wai Lo Lillian Shuk-Nga Chow Ka-Fai To Kwong-Wai Choy Franky Leung Chan Samuel C. Mok Dolly P. Huang |
| author_sort | Joseph Kwong |
| collection | DOAJ |
| description | Aberrant retinoid signaling in human cancers is extending from the nucleus to the cytoplasm. Recently, we have demonstrated frequent epigenetic inactivation of a retinoic acid receptor (RAR), RARβ2, in nasopharyngeal carcinoma (NPC). To further explore targets contributing to aberrant retinoid signaling in NPC, the expression of cellular retinol-binding proteins (CRBPs), cellular retinoic acid-binding proteins (CRABPs), RARs, and retinoid X receptors (RXRs) was examined. Apart from RARβ2, transcriptional silencing of two CRBPs, CRBPI and CRBPIV, was observed in NPC cell lines and xenografts. Hypermethylation of CRBPI and CRBPIV CpG islands was found to be closely correlated with the loss of expression. Treatment with the DNA methyltransferase inhibitor, 5-aza2'-deoxycytidine, resulted in reexpression of CRBPI and CRBPIV gene expression in NPC cell lines. Both CRBPI and CRBPIV hypermethylations were also observed in 43/48 (87.8%) and 26/48 (54.2%) primary NPC tumors, respectively. Here, we reported for the first time that CRBPIV was transcriptionally inactivated by promoter hypermethylation in human cancer. Simultaneous methylation of CRBPI, CRBPIV, and RARβ2 was commonly found in NPC primary tumors. Our findings implied that epigenetic disruption of the CRBPs, CRBPI and CRBPIV, is important in NPC tumorigenesis and may contribute to the loss of retinoic acid responsiveness in cancer. |
| first_indexed | 2024-12-21T14:00:14Z |
| format | Article |
| id | doaj.art-5971aa2be98a43379fb5fcf202247f22 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-21T14:00:14Z |
| publishDate | 2005-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-5971aa2be98a43379fb5fcf202247f222022-12-21T19:01:23ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-01-0171677410.1593/neo.04370Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal CarcinomaJoseph Kwong0Kwok-Wai Lo1Lillian Shuk-Nga Chow2Ka-Fai To3Kwong-Wai Choy4Franky Leung Chan5Samuel C. Mok6Dolly P. Huang7Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, SAR, ChinaDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, SAR, ChinaDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, SAR, ChinaDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, SAR, ChinaDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, ChinaDepartment of Anatomy, The Chinese University of Hong Kong, Hong Kong, SAR, ChinaLaboratory of Gynecologic Oncology, Division of Gynecologic Oncology, Department of Obstetrics, Gynecologic, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, SAR, ChinaAberrant retinoid signaling in human cancers is extending from the nucleus to the cytoplasm. Recently, we have demonstrated frequent epigenetic inactivation of a retinoic acid receptor (RAR), RARβ2, in nasopharyngeal carcinoma (NPC). To further explore targets contributing to aberrant retinoid signaling in NPC, the expression of cellular retinol-binding proteins (CRBPs), cellular retinoic acid-binding proteins (CRABPs), RARs, and retinoid X receptors (RXRs) was examined. Apart from RARβ2, transcriptional silencing of two CRBPs, CRBPI and CRBPIV, was observed in NPC cell lines and xenografts. Hypermethylation of CRBPI and CRBPIV CpG islands was found to be closely correlated with the loss of expression. Treatment with the DNA methyltransferase inhibitor, 5-aza2'-deoxycytidine, resulted in reexpression of CRBPI and CRBPIV gene expression in NPC cell lines. Both CRBPI and CRBPIV hypermethylations were also observed in 43/48 (87.8%) and 26/48 (54.2%) primary NPC tumors, respectively. Here, we reported for the first time that CRBPIV was transcriptionally inactivated by promoter hypermethylation in human cancer. Simultaneous methylation of CRBPI, CRBPIV, and RARβ2 was commonly found in NPC primary tumors. Our findings implied that epigenetic disruption of the CRBPs, CRBPI and CRBPIV, is important in NPC tumorigenesis and may contribute to the loss of retinoic acid responsiveness in cancer.http://www.sciencedirect.com/science/article/pii/S1476558605801009CRBPIVCRBPIretinoidhypermethylationnasopharyngeal carcinoma |
| spellingShingle | Joseph Kwong Kwok-Wai Lo Lillian Shuk-Nga Chow Ka-Fai To Kwong-Wai Choy Franky Leung Chan Samuel C. Mok Dolly P. Huang Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal Carcinoma Neoplasia: An International Journal for Oncology Research CRBPIV CRBPI retinoid hypermethylation nasopharyngeal carcinoma |
| title | Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal Carcinoma |
| title_full | Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal Carcinoma |
| title_fullStr | Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal Carcinoma |
| title_full_unstemmed | Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal Carcinoma |
| title_short | Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal Carcinoma |
| title_sort | epigenetic silencing of cellular retinol binding proteins in nasopharyngeal carcinoma |
| topic | CRBPIV CRBPI retinoid hypermethylation nasopharyngeal carcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S1476558605801009 |
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