Journal
CELLULAR SIGNALLING
Volume 92, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2022.110246
Keywords
Medulloblastoma; Estrogen receptor; Protein kinase C
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Funding
- DGAPA ,UNAM, Mexico [PAPIIT IA201120, PAPIIT IN219719]
- CONACYT [A1-S-18285]
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Medulloblastoma is the most common and aggressive pediatric intracranial tumor. The expression and phosphorylation of estrogen receptor beta (ER beta) are associated with Medulloblastoma development. Protein kinases C (PKCs) alpha and delta have been identified as potential regulators of ER beta through phosphorylation. The activation of ER beta by PKC alpha and PKC delta promotes proliferation and invasion of Medulloblastoma cells.
Medulloblastoma (MB) is the most common and aggressive pediatric intracranial tumor. Estrogen receptor beta (ER beta) expression correlates with MB development and its phosphorylation modifies its transcriptional activity in a ligand-dependent or independent manner. Using in silico tools, we have identified several residues in ER beta protein as potential targets of protein kinases C (PKCs) alpha and delta. Using Daoy cells, we observed that PKC alpha and PKC delta associate with ER beta and induce its phosphorylation. The activation of ER beta promotes MB cells proliferation and invasion, and PKCs downregulation dysregulates these steroid receptor mediated processes. Our data suggest that these kinases may play a crucial role in the regulation of the ER beta transcriptional activity. Overexpression of both PKC alpha and PKC delta in MB biopsies samples supports their relevance in MB progression.
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