Related Experiment Video
Updated: Jul 2, 2026
Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice
Published on: October 3, 2010
Coexpression of neuronatin splice forms promotes medulloblastoma growth
I-Mei Siu1, Renyuan Bai, Gary L Gallia
1Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231 USA.
Abstract:
Medulloblastoma (MB) is the most common pediatric brain cancer. Several important developmental pathways have been implicated in MB formation, but fewer therapeutic targets have been identified. To locate frequently overexpressed genes, we performed a comprehensive gene expression survey of MB. Our comparison of 20 primary tumors to normal cerebellum identified neuronatin (NNAT) as the most frequently overexpressed gene in our analysis. NNAT is a neural-specific developmental gene with alpha and beta splice forms. Functional evaluation revealed that RNA interference knockdown of NNAT causes a significant decrease in proliferation. Conversely, coexpression of both splice forms in NNAT-negative MB cell lines increased proliferation, caused a significant shift from G(1) to G(2)/M, and increased soft agar colony formation and size. When expressed individually, each NNAT splice form had much less effect on these in vitro oncogenic predictors. In an in vivo model, the coexpression of both splice forms conferred the ability of xenograft formation to human MB cells that do not normally form xenografts, whereas a control gene had no effect. Our findings suggest that the frequently observed overexpression of both NNAT splice forms in MB enhances growth in this cancer.
Insights
Neuronatin (NNAT) is frequently overexpressed in pediatric medulloblastoma (MB), a common brain cancer. Overexpression of both NNAT splice forms enhances tumor growth and proliferation, suggesting NNAT as a potential therapeutic target.
Area of Science:
- Oncology
- Neuroscience
- Genetics
Background:
- Medulloblastoma (MB) is the most common pediatric brain cancer, with limited therapeutic targets identified.
- Key developmental pathways are implicated in MB formation, necessitating the discovery of novel oncogenes.
Purpose of the Study:
- To identify frequently overexpressed genes in medulloblastoma through a comprehensive gene expression survey.
- To investigate the role of neuronatin (NNAT) and its splice forms in MB proliferation and oncogenesis.
Main Methods:
- Comparative gene expression analysis of 20 primary MB tumors versus normal cerebellum.
- Functional studies using RNA interference (RNAi) knockdown of NNAT.
- In vitro assays (proliferation, soft agar colony formation) and in vivo xenograft models.
Main Results:
- Neuronatin (NNAT) was identified as the most frequently overexpressed gene in MB.
- NNAT knockdown significantly decreased MB cell proliferation.
- Coexpression of both NNAT splice forms enhanced proliferation, altered cell cycle progression (G1 to G2/M shift), and increased colony formation in vitro.
- Coexpression of both NNAT splice forms enabled xenograft formation in vivo.
Conclusions:
- Overexpression of both NNAT splice forms is common in MB and significantly promotes tumor growth and oncogenic potential.
- NNAT represents a promising therapeutic target for medulloblastoma treatment.
Related Concept Videos
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...