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 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.