title: CDK5 and its activator P35 in normal pituitary and in pituitary adenomas: relationship to VEGF expression.
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.
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Xie
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: He
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002460:Cell Line; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5
keywords: Cdk5; VEGF; expression.; p35; pituitary adenomas