Comparative study of the expression of proteins involved in the cell cycle in renal secondary hyperparathyroidism

Abstract

In renal hyperparathyroidism, parathyroid cell proliferation seems to play a key role in the progression of the disease. Therefore, G1/S transition, a main cell cycle regulatory step, could be deregulated in these patients. One hundred and one parathyroid glands, taken from parathyroidectomies performed on 41 patients on hemodialysis (HD), and 15 glands, taken from 7 patients with post-transplantation persistent hyperparathyroidism (HPT), were studied. Twelve normal parathyroid (PT) glands were used as the control. Biochemical data, immunohistochemical (IHC) profiles of G1/S transition regulators belonging to the two main pathways (cyclin D1/p16INK4A/pRb and p14ARF/p53/MDM2), and proliferation rate (Ki67) were correlated. All of the other proteins differed from normal IHC profiles in both groups that showed significant higher proliferating rates, decreases in p27KIP1, pRb, and cyclin D1, as well as increases in p16INK4A, p53, MDM2, and p21WAF1 levels, in comparison with normal PT glands, with the exception of cyclin D3. Contrary to patients with HPT who were on hemodialysis, in post-transplantation HPT, consistent correlations between biochemical data and IHC profiles were obtained. In both groups IHC profiles of proteins involved in G1/S transition regulation significantly differed from normal PT glands. The results support partial reversion to normal IHC profile in post-transplantation HPT.