SCCRO promotes glioma formation and malignant progression in mice

Stephen R. Broderick, Benjamin J. Golas, Mimi Ceppa, Christopher W. Towe, Simon G. Talbot, Andrew Kaufman, Sarina Bains, Laryssa A. Huryn, Yoshihiro Yonekawa, Diane Carlson, Dolores Hambardzumyan, Yegnanarayana Ramanathan, Bhuvanesh Singh

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)476-484
Number of pages9
JournalNeoplasia
Volume12
Issue number6
StatePublished - 2010
Externally publishedYes

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Glioma
Oncogenes
Neoplasms
Platelet-Derived Growth Factor
Glioblastoma
Squamous Cell Carcinoma
Nestin
Oncogenic Viruses
Terminal Repeat Sequences
Heterografts
Nude Mice
Neuroglia
Stem Cells
Cell Culture Techniques
Ectopic Gene Expression

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

Cite this

Broderick, S. R., Golas, B. J., Ceppa, M., Towe, C. W., Talbot, S. G., Kaufman, A., ... Singh, B. (2010). SCCRO promotes glioma formation and malignant progression in mice. Neoplasia, 12(6), 476-484.

SCCRO promotes glioma formation and malignant progression in mice. / Broderick, Stephen R.; Golas, Benjamin J.; Ceppa, Mimi; Towe, Christopher W.; Talbot, Simon G.; Kaufman, Andrew; Bains, Sarina; Huryn, Laryssa A.; Yonekawa, Yoshihiro; Carlson, Diane; Hambardzumyan, Dolores; Ramanathan, Yegnanarayana; Singh, Bhuvanesh.

In: Neoplasia, Vol. 12, No. 6, 2010, p. 476-484.

Research output: Contribution to journalArticle

Broderick, SR, Golas, BJ, Ceppa, M, Towe, CW, Talbot, SG, Kaufman, A, Bains, S, Huryn, LA, Yonekawa, Y, Carlson, D, Hambardzumyan, D, Ramanathan, Y & Singh, B 2010, 'SCCRO promotes glioma formation and malignant progression in mice', Neoplasia, vol. 12, no. 6, pp. 476-484.
Broderick SR, Golas BJ, Ceppa M, Towe CW, Talbot SG, Kaufman A et al. SCCRO promotes glioma formation and malignant progression in mice. Neoplasia. 2010;12(6):476-484.
Broderick, Stephen R. ; Golas, Benjamin J. ; Ceppa, Mimi ; Towe, Christopher W. ; Talbot, Simon G. ; Kaufman, Andrew ; Bains, Sarina ; Huryn, Laryssa A. ; Yonekawa, Yoshihiro ; Carlson, Diane ; Hambardzumyan, Dolores ; Ramanathan, Yegnanarayana ; Singh, Bhuvanesh. / SCCRO promotes glioma formation and malignant progression in mice. In: Neoplasia. 2010 ; Vol. 12, No. 6. pp. 476-484.
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AU - Bains, Sarina

AU - Huryn, Laryssa A.

AU - Yonekawa, Yoshihiro

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