Association of overexpressed proline-directed protein kinase F(A) with chemoresistance, invasion, and recurrence in patients with bladder carcinoma.
BACKGROUND
It has been shown previously that proline-directed protein kinase F(A) (PDPK F(A)) is overexpressed in various human malignancies compared with its expression in normal controls, and the suppression of overexpressed PDPK F(A) is capable of inhibiting the growth of various types of human carcinoma cells, suggesting a role for this PDPK in human malignancies. In this report, the authors combine immunohistologic, molecular, cellular, and clinicopathologic studies to demonstrate further an essential critical role for overexpressed PDPK F(A) in bladder carcinoma invasion, chemoresistance, and poor prognosis.


METHODS
The expression and localization of PDPK F(A) were analyzed by the immunohistochemical staining of specimens obtained from patients with primary transitional cell carcinoma (TCC) of the bladder. The stable antisense clones of human bladder carcinoma cells with specific suppression of overexpressed PDPK F(A) were established for invasion and chemosensitivity studies.


RESULTS
The immunohistochemical study revealed that PDPK F(A) was overexpressed preferentially in the invasive bladder carcinoma tissues. It was found that the stable antisense clones with specific suppression of overexpressed PDPK F(A) to approximately 40% of the parental control level were capable of inhibiting the invasive activity and simultaneously enhancing the chemosensitivity of bladder carcinoma cells to various therapeutic drugs, such as vinblastine, vincristine, paclitaxel, and bleomycin. Clinicopathologic studies also revealed a correlation between overexpressed PDPK F(A) and disease recurrence/survival in patients with primary TCC (P < 0.05).


CONCLUSIONS
Taken together, the results demonstrate an essential critical role of overexpressed PDPK F(A) in invasion, chemoresistance, and poor prognosis. Suppression of overexpressed PDPK F(A) may provide a new potential target for therapeutic intervention aimed at preventing chemoresistance, disease progression, and recurrence in patients with bladder carcinoma.
Hsueh
Sheng-Fen
SF
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
Lai
Ming-Tsung
MT
Yang
Chuan-Ching
CC
Chung
Yuan-Chiang
YC
Hsu
Chih-Ping
CP
Peng
Chien-Chung
CC
Fu
Hsiao-Hui
HH
Cheng
Yung-Ming
YM
Chang
King-Jen
KJ
Yang
Shiaw-Der
SD
D000328:Adult; D000368:Aged; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3