HuR in pheochromocytomas and paragangliomas – overexpression in verified malignant tumors

Abstract

Pheochromocytomas and paragangliomas are rare, neural crest-originating, neuroendocrine tumors. HuR is an mRNA-binding protein of the ELAV/Hu-protein family, which participates in posttranscriptional regulation of many cancer-associated genes. HuR expression has been connected with aggressive behavior of several malignancies. Cyclooxygenase-2 (COX-2) is also expressed in several malignant tumors, and its expression is regulated by HuR. Tissue microarray of 153 primary pheochromocytomas and paragangliomas was investigated for the expression of HuR and COX-2 proteins by immunohistochemistry using two different HuR antibodies (HuR19F12 and HuR3A). In these tumors, the expression of both intranuclear and cytoplasmic HuR was detectable. Increased cytoplasmic HuR expression was significantly associated with metastatic tumors. Increased COX-2 and MIB-1 expression also was associated with metastatic potential, and moreover, HuR and COX-2 expression correlated with each other. Our data suggest that increased expression of HuR protein is associated with metastatic potential of paragangliomas and pheochromocytomas, and COX-2 seems to be a target of HuR.

Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors

“…The five mutations p.Arg161Gln, p.Gln164His, p.Val166Phe, Arg167Trp and Arg167Gln localize in a small area forming the ELAVL1 binding interface (Fig 5). Increased expression of this protein was recently proposed [68] to be linked with the metastatic potential of both paraganglioma and pheochromocytoma. Similarly, the three mutations p.His115Arg, p.Trp117Gly and p.Ile151Phe localize on the androgen receptor (AR) binding interface, suggesting that these specific interactors may play a crucial role in cystadenoma insurgence (Fig 5).…”

Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18

“…These in vitro study results provide an impetus for testing HuR-FNP in vivo either as a monotherapy or in combination therapy with conventional chemotherapeutics and other molecular targeted therapies for lung cancer. A study by Leijon et al [ 22 ] showed that increased expression of HuR protein is associated with metastatic potential of paragangliomas and pheochromocytomas, and cyclooxygenase 2 (COX-2) was identified as a target of HuR. In many malignancies, HuR expression is associated with high grade, poor prognosis, and large tumor size [ 23 ].…”