SCCRO Promotes Glioma Formation and Malignant Progression in Mice
Originally identified as an oncogene activated by amplification in squamous cell carcinomas, several lines of evidence now suggest that squamous cell carcinoma-related oncogene (SCCRO; aka DCUN1D1) may play a role in the pathogenesis of a wide range of human cancers including gliomas. SCCRO's o...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558610800053 |
| _version_ | 1818565192203632640 |
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| author | Stephen R. Broderick Benjamin J. Golas Duykhanh Pham Christopher W. Towe Simon G. Talbot Andrew Kaufman Sarina. Bains Laryssa A. Huryn Yoshihiro Yonekawa Diane Carlson Dolores Hambardzumyan Yegnanarayana Ramanathan Bhuvanesh Singh |
| author_facet | Stephen R. Broderick Benjamin J. Golas Duykhanh Pham Christopher W. Towe Simon G. Talbot Andrew Kaufman Sarina. Bains Laryssa A. Huryn Yoshihiro Yonekawa Diane Carlson Dolores Hambardzumyan Yegnanarayana Ramanathan Bhuvanesh Singh |
| author_sort | Stephen R. Broderick |
| collection | DOAJ |
| description | Originally identified as an oncogene activated by amplification in squamous cell carcinomas, several lines of evidence now suggest that squamous cell carcinoma-related oncogene (SCCRO; aka DCUN1D1) may play a role in the pathogenesis of a wide range of human cancers including gliomas. SCCRO's oncogenic function is substantiated by its ectopic expression, resulting in transformation of cells in culture and xenograft formation in nude mice. The aim of this study was to assess the in vivo oncogenicity of SCCRO in a murine model. Ubiquitous expression of SCCRO resulted in early embryonic lethality. Because SCCRO overexpression was detected in human gliomas, its in vivo oncogenic activity was assessed in an established murine glioma model. Conditional expression of SCCRO using a replication-competent ASLV long terminal repeat with splice acceptor/nestin-(tumor virus-A) tv-a model system was not sufficient to induce tumor formation in a wild-type genetic background, but tumors formed with increasing frequency and decreasing latency in facilitated background containing Ink4a deletion alone or in combination with PTEN loss. Ectopic expression of SCCRO in glial progenitor cells resulted in lower-grade gliomas in Ink4a-/- mice, whereas its expression in Ink4a-/-/PTEN-/- background produced high-grade glioblastoma-like lesions that were indistinguishable from human tumors. Expression of SCCRO with platelet-derived growth factor-beta (PDGF-β) resulted in an increased proportion of mice forming glioblastoma-like tumors compared with those induced by PDGF-β alone. This work substantiates SCCRO's function as an oncogene by showing its ability to facilitate malignant transformation and carcinogenic progression in vivo and supports a role for SCCRO in the pathogenesis of gliomas and other human cancers. |
| first_indexed | 2024-12-14T01:38:05Z |
| format | Article |
| id | doaj.art-176a8216b533461d8da1bd493df5dcb2 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-14T01:38:05Z |
| publishDate | 2010-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-176a8216b533461d8da1bd493df5dcb22022-12-21T23:21:49ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022010-06-0112647648410.1593/neo.10202SCCRO Promotes Glioma Formation and Malignant Progression in MiceStephen R. Broderick0Benjamin J. Golas1Duykhanh Pham2Christopher W. Towe3Simon G. Talbot4Andrew Kaufman5Sarina. Bains6Laryssa A. Huryn7Yoshihiro Yonekawa8Diane Carlson9Dolores Hambardzumyan10Yegnanarayana Ramanathan11Bhuvanesh Singh12Thoracic Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThoracic Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThoracic Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThoracic Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThe Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThoracic Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThe Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThe Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThe Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThe Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAProgram in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThe Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAThe Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USAOriginally identified as an oncogene activated by amplification in squamous cell carcinomas, several lines of evidence now suggest that squamous cell carcinoma-related oncogene (SCCRO; aka DCUN1D1) may play a role in the pathogenesis of a wide range of human cancers including gliomas. SCCRO's oncogenic function is substantiated by its ectopic expression, resulting in transformation of cells in culture and xenograft formation in nude mice. The aim of this study was to assess the in vivo oncogenicity of SCCRO in a murine model. Ubiquitous expression of SCCRO resulted in early embryonic lethality. Because SCCRO overexpression was detected in human gliomas, its in vivo oncogenic activity was assessed in an established murine glioma model. Conditional expression of SCCRO using a replication-competent ASLV long terminal repeat with splice acceptor/nestin-(tumor virus-A) tv-a model system was not sufficient to induce tumor formation in a wild-type genetic background, but tumors formed with increasing frequency and decreasing latency in facilitated background containing Ink4a deletion alone or in combination with PTEN loss. Ectopic expression of SCCRO in glial progenitor cells resulted in lower-grade gliomas in Ink4a-/- mice, whereas its expression in Ink4a-/-/PTEN-/- background produced high-grade glioblastoma-like lesions that were indistinguishable from human tumors. Expression of SCCRO with platelet-derived growth factor-beta (PDGF-β) resulted in an increased proportion of mice forming glioblastoma-like tumors compared with those induced by PDGF-β alone. This work substantiates SCCRO's function as an oncogene by showing its ability to facilitate malignant transformation and carcinogenic progression in vivo and supports a role for SCCRO in the pathogenesis of gliomas and other human cancers.http://www.sciencedirect.com/science/article/pii/S1476558610800053 |
| spellingShingle | Stephen R. Broderick Benjamin J. Golas Duykhanh Pham Christopher W. Towe Simon G. Talbot Andrew Kaufman Sarina. Bains Laryssa A. Huryn Yoshihiro Yonekawa Diane Carlson Dolores Hambardzumyan Yegnanarayana Ramanathan Bhuvanesh Singh SCCRO Promotes Glioma Formation and Malignant Progression in Mice Neoplasia: An International Journal for Oncology Research |
| title | SCCRO Promotes Glioma Formation and Malignant Progression in Mice |
| title_full | SCCRO Promotes Glioma Formation and Malignant Progression in Mice |
| title_fullStr | SCCRO Promotes Glioma Formation and Malignant Progression in Mice |
| title_full_unstemmed | SCCRO Promotes Glioma Formation and Malignant Progression in Mice |
| title_short | SCCRO Promotes Glioma Formation and Malignant Progression in Mice |
| title_sort | sccro promotes glioma formation and malignant progression in mice |
| url | http://www.sciencedirect.com/science/article/pii/S1476558610800053 |
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