Endocrine Abstracts

Background

Recent data have shown the anti-apoptotic effect of Chchd2 mitochondrial protein through the Bcl-2/Bax pathway in various cancers. Bax is regulated primarily by proteins-members of Bcl-2 family and mainly the Bcl-2 protein, which has been found to prevent Bax from accumulating in mitochondria. In response to apoptotic stimuli, Chchd2 decreases and loses its mitochondria localization accompanying by decreased Bcl-2/Bax interaction and increased Bax homo-oligomerization. Thus, Chchd2 negatively regulates the apoptotic cascade upstream of Bax oligomerization. Although, the direct interaction of antiapoptotic Bcl-2 with Bax protein has already been studied, data on the regulatory role of Chchd2 on the expression of Bcl-2/Bax are scarce.

Aim

We aimed to study the expression of CHCHD2, BCL2 and BAX genes at mRNA and protein level in human adrenocortical neoplasms.

Methods

Twenty-four fresh frozen human adrenal tissues including 7 cortisol-secreting adenomas (CSAs), 9 non-functional adrenal adenomas (NFAs) and 8 adrenocortical carcinomas (ACCs) samples were collected. CHCHD2, BCL2 and BAX mRNA and protein expression were determined by qPCR and immunobloting, respectively. The expression of the abovementioned genes was compared with the paired adjacent normal adrenal tissues used as control group.

Results

BCL2 mRNA expression was significantly up-regulated in ACCs compared to benign adrenocortical neoplasms and adjacent normal tissues. BCL2 mRNA expression was up-regulated in all benign adrenocortical neoplasms compared to their paired adjacent normal tissues without reaching however statistical significance. BAX mRNA expression was significantly down-regulated in ACCs compared with benign adrenocortical neoplasms and adjacent normal adrenal tissues. BAX mRNA expression was also down-regulated in all benign adrenocortical neoplasms compared with their paired adjacent normal tissues, although not statistical significant. CHCHD2 mRNA expression was significantly up-regulated in ACCs compared to normal adrenal tissues. CHCHD2 mRNA expression was also up-regulated in all benign adrenocortical neoplasms compared with their paired adjacent tissue although not statistical significant. Western Blot analysis confirmed the results of qPCR analysis.

Conclusions

This study showed that the expression of both BAX and BCL2 apoptotic genes was altered in adrenocortical neoplasms compared to adjacent normal tissues implying a disturbance of the apoptotic pathway in these neoplasms and perhaps in adrenal tumorigenesis. Moreover, the significant overexpression of CHCHD2 in ACCs could contribute to the understanding of its role in the clinical behaviour of these neoplasms although functional studies with a larger sample size are required.