Implication of the Wnt/β-catenin signaling pathway activation in the adenoma and in the malignant adrenocortical cancer
Barbara Czarnocka1, Anna Kasperlik-Zaluska2, Krzysztof Bardadin1, Katarzyna Roszkowska1 & Andrzej Cichocki1
The commonly expressed multifunctional protein and protooncogene β-catenin displays important functions in cellcell adhesion and in the Wnt signaling pathway. Transforming activity of the Wnt/β-catenin pathway is thought to be involved in the development of a variety of human cancers and many β-catenin target genes have been shown to play critical functions in tumors. Therefore, the aim of this project was to determine the expression levels and cellular distribution of active β-catenin and its target genes cyclin D1 and NrCAM a neuronal cell adhesion molecule in adrenocortical tumors. In this study, we performed the immunochistochemistry (IHC) for 13 and 31 patients with adenocortical adenoma (ACA) and carcinoma (ACC), respectively to evaluate the expression levels and subcellular localization of cyclin D1 and NrCAM. At the invasion front of 30/31 ACC cases strong active β-catenin expression was found in the nuclei and cytoplasm of tumor cells and weak expression at the central part of the tumor. Under these conditions, β-catenin can function as a transcription factor and thus activate target genes, among them cyclin D1-cell cycle progression protein and neuronal cell adhesion molecule NrCAM protein involved in the adhesion and signaling. Cyclin D1 low (>5%) to absent in all adrenal tumors. In normal adrenal gland distinct expression of NrCAM was seen in the central part of the cortex and weak on the periphery. In the ACA moderate cytoplasmic NrCAM l was seen through the tumor whereas the in ACC expression level of NrCAM protein was very strong at the invasion front of the cancer in contrast to central part with faint reactivity, suggesting its translocation. Moreover, NrCAM expression was not related to the primary tumor stage or the size. These data suggest that NrCAM, neuronal cell adhesion molecule could be implicated in the pathogenesis and behavior of adrenal tumors.
Grant CMKP 501-1-1-22-01/07.