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

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.

ENPP2 Methylation in Health and Cancer

“…It should be noted that many authors have demonstrated that the relationship between mRNA expression and protein differs in many cancers. It has been reported in lung cancer and glioblastoma that, for many genes, mRNA expression is lower but protein levels are higher compared with the control [ 50 , 51 , 52 , 53 ].…”

Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer

“…Astrocytoma malignancies are positively correlated with progesterone receptor (PR) and PKCα levels as well as with the intracellular colocalization of these proteins. Patients with astrocytoma grades III and IV with low expression of PGR and PRKCA mRNA showed higher survival than those with high expression [ 72 ]. Treatment with mTOR inhibitors (rapamycin, temsirolimus, torin-1, and PP242) reduces glioblastoma progression by reducing invasion, migration, and matrix metalloproteinase (MMP) activity (MMP2 and MMP9) through the reduction of PKCα and NF-κB signaling pathways [ 73 ].…”

Rapid Actions of the Nuclear Progesterone Receptor through cSrc in Cancer

“…Khalid et al found that the protein content of the PR was higher in GBs (grade IV gliomas) than in grade I and II gliomas from the biopsies of 86 patients [ 54 ]. Recently, Arcos-Montoya et al reported that the PR content, determined with immunofluorescence, was higher in samples derived from patients with GBs than in samples from patients with lower-grade gliomas or normal tissue [ 55 ]. In addition to the positive correlation between protein expression and grade of malignancy in gliomas, there is functional evidence of the PR’s role in the progression of GBs.…”