Angiotensin-converting enzymes (ACE and ACE2) are downregulated in renal tumors

The angiotensin-converting enzymes (ACE and ACE2) are highly expressed in renal tubules and play an important role in the regulation of renal function by the intrarenal renin-angiotensin system (iRAS). Dysregulation of these cell-surface peptidases has been associated with renal injury. Most of these studies, however, have focused on non-neoplastic kidney diseases. In the present study, ACE and ACE2 activity and protein and mRNA expression were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytoma (RO). Enzyme activity was measured by spectrofluorometric (ACE2) and spectrophotometric assays (ACE), and protein and mRNA expression were determined by immunohistochemistry and qRT-PCR assays, respectively. The enzyme activities and immunohistochemistry showed that both enzymes are mainly downregulated in these neoplasms. qRT-PCR studies in CCRCC showed no positive correlation between ACE and ACE2 activity/protein expression and mRNA levels, whereas downregulation of ACE2 mRNA levels was observed in tumors from the distal nephron (ChRCC and RO). These findings suggest a metabolic imbalance in iRAS and a role of this system in renal neoplastic diseases, and point to ACE and ACE2 as potential prognostic/diagnostic markers.