α1Connexin 43 Gap Junctions Are Decreased in Human Adrenocortical Tumors1

Gap junctional communication disorders have been implicated in the etiology of benign and malignant tumors. Understanding the type, distribution, and frequency of gap junctions in adrenal disorders should provide insight into the role of gap junctions in adrenal carcinogenesis as well as information that may be useful in developing improved diagnosis and treatment of adrenal diseases. Using immunocytochemical techniques, we have characterized and compared alpha1 connexins 43 gap junction protein levels in normal adrenal glands to those in benign and malignant adrenocortical human tumors. In addition, gap junction protein levels were studied in a human adrenal cancer cell line (H295). In both normal and neoplastic adrenal tissues, only alpha1 connexin 43 could be detected, whereas beta1 connexin 32 and beta2 connexin 26 were not found. In the normal adrenal gland, the zona fasciculata was demonstrated to have the highest number of gap junctions per cell (mean +/- SEM, 13.78 +/- 1.93). In contrast, in benign adrenocortical adenomas, the number of gap junctions per cell compared to that detected in normal adrenal glands was significantly reduced (mean +/- SEM, 4.6 +/- 1.17; P < or = 0.05), and the lowest number was found in malignant adrenocortical tumors (1.42 +/- 0.58; P < or = 0.05). Similarly, there were few or no alpha1 connexin 43 gap junctions in the H295 population. There was a progressive decrease in gap junction plaques in adrenocortical cancer cell populations compared to those in normal cell populations. Therefore, analysis of gap junction protein may be helpful for the differential diagnosis of benign and malignant adrenal tumors. The induction of gap junctions in malignant cells may provide a novel therapeutic strategy for adrenal cancer.