Bmi-1 is essential for the tumorigenicity of neuroblastoma cells

Hongjuan Cui, Bo Hu, Tai Li, Jun Ma, Goleeta Alam, William T. Gunning, Hanfei Ding

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Activation of oncogenes underlies the pathogenesis of most human cancers. In neuroblastoma, amplification of the oncogene MYCN occurs in ∼22% of cases and is associated with advanced stages of the disease and poor prognosis. Identification of other oncogenes that are consistently mutated or overexpressed in neuroblastoma is crucial for a molecular understanding of the pathogenic process. Here, we report that the oncogene Bmi-1 is highly expressed in human neuroblastoma cell lines and primary tumors. Neuroblastoma development in MYCN transgenic mice, an animal model for the human disease, was associated with a marked increase in the levels of Bmi-1 expression. Bmi-1 cooperated with MYCN in transformation of benign S-type neuroblastoma cells and avian neural crest cells by inhibiting the apoptotic activity of MYCN. Importantly, down-regulation of Bmi-1 impaired the ability of neuroblastoma cells to grow in soft agar and induce tumors in immunodeficient mice. Moreover, Bmi-1-knockdown neuroblastoma xenografts were characterized by a significant increase in the amount of Schwannian stroma, a histological feature associated with clinically favorable neuroblastomas. These findings suggest a crucial role for Bmi-1 in neuroblastoma pathogenesis and provide insights into the molecular basis of neuroblastoma heterogeneity.

Original languageEnglish (US)
Pages (from-to)1370-1378
Number of pages9
JournalAmerican Journal of Pathology
Volume170
Issue number4
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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Neuroblastoma
Oncogenes
Genetically Modified Animals
Neural Crest
Tumor Cell Line
Heterografts
Transgenic Mice
Agar
Neoplasms
Down-Regulation
Animal Models

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Bmi-1 is essential for the tumorigenicity of neuroblastoma cells. / Cui, Hongjuan; Hu, Bo; Li, Tai; Ma, Jun; Alam, Goleeta; Gunning, William T.; Ding, Hanfei.

In: American Journal of Pathology, Vol. 170, No. 4, 01.01.2007, p. 1370-1378.

Research output: Contribution to journalArticle

Cui, Hongjuan ; Hu, Bo ; Li, Tai ; Ma, Jun ; Alam, Goleeta ; Gunning, William T. ; Ding, Hanfei. / Bmi-1 is essential for the tumorigenicity of neuroblastoma cells. In: American Journal of Pathology. 2007 ; Vol. 170, No. 4. pp. 1370-1378.
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