Progesterone Receptor Together with PKCα Expression as Prognostic Factors for Astrocytomas Malignancy

Onco Targets Ther. 2021 Jun 16:14:3757-3768. doi: 10.2147/OTT.S280314. eCollection 2021.

Abstract

Introduction: Astrocytomas are the most common and aggressive primary brain tumors, and they are classified according to the degree of malignancy on a scale of I to IV, in which grade I is the least malignant and grade IV the highest. Many factors are related to astrocytomas progression as progesterone receptor (PR), whose transcriptional activity could be regulated by phosphorylation by protein kinase C alpha (PKCα) at the residue Ser400. Our aim was to investigate if PR phosphorylation together with PKCα expression could be used as a prognostic factor for astrocytomas malignancy.

Methods: By immunofluorescence, we detected the content of PKCα, PR and its phosphorylation at Ser400 in 46 biopsies from Mexican patients with different astrocytoma malignancy grades; by bioinformatic tools using TCGA data, we evaluated the expression of PR and PKCα mRNA according to astrocytoma malignancy grades. For all statistical analyses, significance was p<0.05.

Results: We detected a positive correlation between the tumor grade and the content of PKCα, PR and its phosphorylation at Ser400, as well as the intracellular colocalization of these proteins. Interestingly, using an in silico assay, we found that the PR and PKCα expression at mRNA level has an inverse ratio with astrocytomas tumor grade.

Discussion: These results indicate that PR and its phosphorylation at Ser400 site, as well as PKCα and their colocalization, could be considered as possible malignancy biomarkers for astrocytomas grades I-IV.

Keywords: astrocytoma; biomarker; glioblastoma; progesterone receptor; protein kinase C alpha.

Grants and funding

This work was supported by Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) IA201120 and IN219719. Denisse Arcos-Montoya is a PhD student from Programa de Maestría y Doctorado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM) and received fellowship 894557 from CONACyT.