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A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
CDK5 and its activator P35 in normal pituitary and in pituitary adenomas: relationship to VEGF expression
Weiyan Xie1, Hongyun Wang1, Yue He1
1Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
Abstract:
Pituitary tumors are monoclonal adenomas that account for about 10-15% of intracranial tumors. Cyclin-dependent kinase 5 (CDK5) regulates the activities of various proteins and cellular processes in the nervous system, but its potential roles in pituitary adenomas are poorly understood. The kinase activity of CDK5 requires association with an activating protein, p35 (also known as CDK5 activator 1, p35). Here, we show that functional CDK5, associated with p35, is present in normal human pituitary and in pituitary tumors. Furthermore, p35 mRNA and protein levels were higher in pituitary adenomas than in the normal glands, suggesting that CDK5 activity might be upregulated in pituitary tumors. Inhibition of CDK5 activity in rat pituitary cells, reduced the expression of vascular endothelial growth factor (VEGF), a protein that regulates vasculogenesis and angiogenesis. Our results suggest that increased CDK5-mediated VEGF expression might play a crucial role in the development of pituitary adenomas, and that roscovitine and other CDK5 inhibitors could be useful as anticancer agents.
Insights
Cyclin-dependent kinase 5 (CDK5) and its activator p35 are present in pituitary tumors. Inhibiting CDK5 reduces vascular endothelial growth factor (VEGF), suggesting CDK5 inhibitors may treat pituitary adenomas.
Area of Science:
- Neuro-oncology
- Molecular biology
- Endocrinology
Background:
- Pituitary tumors, accounting for 10-15% of intracranial tumors, are monoclonal adenomas.
- Cyclin-dependent kinase 5 (CDK5) is crucial in nervous system regulation, but its role in pituitary adenomas is unclear.
- CDK5 requires the p35 protein (CDK5 activator 1) for its kinase activity.
Purpose of the Study:
- To investigate the presence and role of functional CDK5 and p35 in normal pituitary glands and pituitary tumors.
- To explore the potential impact of CDK5 activity on vascular endothelial growth factor (VEGF) expression in pituitary cells.
- To evaluate CDK5 inhibitors as potential therapeutic agents for pituitary adenomas.
Main Methods:
- Detection of functional CDK5/p35 complex in normal human pituitary and pituitary tumor tissues.
- Quantification of p35 mRNA and protein levels in pituitary adenomas versus normal glands.
- Inhibition of CDK5 activity in rat pituitary cells and assessment of downstream effects on VEGF expression.
Main Results:
- Functional CDK5, complexed with p35, was identified in both normal pituitary tissue and pituitary tumors.
- Pituitary adenomas exhibited significantly higher p35 mRNA and protein levels compared to normal glands.
- Inhibition of CDK5 activity in rat pituitary cells led to a notable reduction in VEGF expression.
Conclusions:
- Increased CDK5 activity, potentially due to elevated p35 levels, may contribute to pituitary adenoma development.
- CDK5-mediated regulation of VEGF expression appears to be a key factor in pituitary tumorigenesis.
- CDK5 inhibitors, such as roscovitine, show promise as potential anticancer agents for treating pituitary adenomas.
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