■星形细胞瘤是最常见和侵袭性的原发性脑肿瘤,根据恶性程度分为I至IV级,其中I级最不恶性,IV级最高。许多因素与星形细胞瘤进展有关,如孕激素受体(PR),其转录活性可以通过蛋白激酶Cα(PKCα)在Ser400残基处的磷酸化来调节。我们的目的是研究PR磷酸化与PKCα表达是否可以用作星形细胞瘤恶性肿瘤的预后因素。
■通过免疫荧光,我们检测到PKCα的含量,来自不同星形细胞瘤恶性程度的墨西哥患者的46个活检组织的PR及其在Ser400的磷酸化;通过使用TCGA数据的生物信息学工具,我们根据星形细胞瘤的恶性程度评估PR和PKCαmRNA的表达。对于所有统计分析,显著性为p<0.05。
■我们检测到肿瘤分级与PKCα含量呈正相关,PR及其在Ser400的磷酸化,以及这些蛋白质的细胞内共定位。有趣的是,使用计算机模拟检测,我们发现mRNA水平的PR和PKCα表达与星形细胞瘤的肿瘤分级成反比。
■这些结果表明PR及其在Ser400位点的磷酸化,以及PKCα和它们的共定位,可被认为是星形细胞瘤I-IV级的可能的恶性肿瘤生物标志物。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.