Overexpression of cyclin-dependent kinase-associated protein phosphatase enhances cell proliferation in renal cancer cells

Objective: The aim of this study was to understand the role of cyclin-dependent kinase-associated protein phosphatase (KAP) in renal cancer cell growth. Materials and methods: Renal cell carcinoma (RCC) tissues from 58 patients receiving surgical resection were included for immunohistochemistry analysis. Additionally, human embryonic kidney (HEK293) cells overexpressing KAP were established for tumorigenicity experiments. Results: Clinicopathologic analysis indicated that poorly differentiated RCCs with a higher histological grade (grade 3/4) were associated with a higher proportion of KAP-positive cells (P < 0.001) as well as cytoplasmic expression of KAP (P < 0.05). HEK293 cells overexpressine KAP had a higher growth rate, greater resistance to TNF-alpha mediated increment of caspase 3 activity, a shorter cell cycle time, and greater ability of cell invasion. Tumorigenicity experiments showed that KAP-overexpressing cells generated significantly larger xenograft tumors in nude mice compared with mock controls (P = 0.032). Conclusions: KAP expression was associated with poorly differentiated RCCs and overexpression of KAP in renal cells enhanced cell proliferation, resistance to apoptosis, invasive ability, and xenograft tumor formation. (C) 2012 Elsevier Inc. All rights reserved.