The Relationship Between cAMP Responsive Element Binding Protein and Its Phosphorylated Form in Cardiac Myxoma with DNA Mutation of Protein Kinase cAMP-Dependent Type I Regulatory Subunit Alpha

Abstract

Considering the lack of information regarding the role and mechanism of low expression of PRKAR1α in cardiac myxoma, we investigated the relationship between the low expression of PRKAR1α and the cAMP responsive element binding protein (CREB) and the expression of its phosphorylated form (p-CREB) in cardiac myxoma tissue. For this purpose, we conducted a retrospective analysis of 130 cases of CM tissue obtained by surgical resection, from which paraffin-fixed tissue DNA was extracted, followed by detection of PRKAR1A DNA mutation by Sanger sequencing and detection of CREB, p-CREB, and PKAR1α protein expression by immunohistochemical SP method. Mutations in the PRKAR1A gene coding region were detected in 35 (46.05%) of 76 sporadic CM tissues, of which 48.57% (17/35 cases) had more than two mutations, and 28.57% (10/35 cases) had exon4: C.349-4-C.349-5insertTmutation. Compared with the surrounding normal tissues, 55.26% (42/76 cases) of PKAR1α protein was not expressed or weakly expressed, CREB was not expressed in myxoma and myocardial tissues, p-CREB was expressed in 51 (67.11%) CM-positive tissues, and PKAR1α and p-CREB expression demonstrated no correlation (P > 0.05). These results indicate the presence of a high level of CREB phosphorylation in cardiac myxoma tissue; however, its phosphorylation is not associated with mutations in the PRKAR1A gene coding region and PKAR1α expression.