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

Abstract

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 overexpressing KAP had a higher growth rate, greater resistance to TNF-α 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.