期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 170, 期 4, 页码 1370-1378出版社
AMER SOC INVESTIGATIVE PATHOLOGY, INC
DOI: 10.2353/ajpath.2007.060754
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资金
- NATIONAL CANCER INSTITUTE [K01CA078534, R01CA106550] Funding Source: NIH RePORTER
- NCI NIH HHS [CA78534, R01 CA106550, CA106550] Funding Source: Medline
Activation of oncogenes underlies the pathogenesis of most human cancers. In neuroblastoma, amplification of the oncogene MYCN occurs in similar to 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.
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