SCCRO promotes glioma formation and malignant progression in mice Journal Article
| Authors: | Broderick, S. R.; Golas, B. J.; Pham, D.; Towe, C. W.; Talbot, S. G.; Kaufman, A.; Bains, S.; Huryn, L. A.; Yonekawa, Y.; Carlson, D.; Hambardzumyan, D.; Ramanathan, Y.; Singh, B. |
| Article Title: | SCCRO promotes glioma formation and malignant progression in mice |
| Abstract: | 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 trans-formation and carcinogenic progression in vivo and supports a role for SCCRO in the pathogenesis of gliomas and other human cancers. © 2010 Neoplasia Press, Inc. |
| Keywords: | platelet derived growth factor; controlled study; human tissue; unclassified drug; oncoprotein; human cell; gene deletion; proto-oncogene proteins; cancer growth; nonhuman; glioma; brain neoplasms; cancer grading; animal cell; mouse; animals; mice; mice, knockout; animal tissue; gene overexpression; embryo; animal experiment; gene function; cell differentiation; neurons; wild type; mice, inbred c57bl; carcinogenesis; mice, transgenic; immunoenzyme techniques; oncogene; blotting, western; reverse transcriptase polymerase chain reaction; rna, messenger; glioblastoma; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; cancer stem cell; carcinogenicity; pten phosphohydrolase; proto-oncogene proteins c-sis; gene loss; embryonic stem cells; cyclin dependent kinase inhibitor 2a; cyclin-dependent kinase inhibitor p16; malignant transformation; nestin; gene activity; genes, lethal; gene replication; platelet derived growth factor beta; squamous cell carcinoma related oncoprotein |
| Journal Title: | NeoPlasia |
| Volume: | 12 |
| Issue: | 6 |
| ISSN: | 1522-8002 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2010-06-01 |
| Start Page: | 476 |
| End Page: | 484 |
| Language: | English |
| PUBMED: | 20563250 |
| PROVIDER: | scopus |
| PMCID: | PMC2887088 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: NEOPF" - "Source: Scopus" |
Citation Impact
MSK Authors
Related MSK Work