To isolate novel diagnostic markers and therapeutic targets for
pancreatic cancer, we earlier did expression profile analysis of
pancreatic cancer cells using a genome-wide
cDNA microarray combined with microdissection. Among dozens of trans-activated genes in
pancreatic cancer cells, this study focused on KIAA0101 whose overexpression in
pancreatic cancer cells was validated by immunohistochemical analysis. KIAA0101 was previously identified as p15(PAF) [
proliferating cell nuclear antigen (
PCNA)-associated factor] to bind with
PCNA; however, its function remains unknown. To investigate for the biological significance of KIAA0101 overexpression in
cancer cells, we knocked down KIAA0101 by
small interfering RNA (
siRNA) in
pancreatic cancer cells and found that the reduced expression by
siRNA caused drastic attenuation of their proliferation as well as significant decrease in DNA replication rate. Concordantly, exogenous overexpression of KIAA0101 enhanced
cancer cell growth, and NIH3T3 derivative cells expressing KIAA0101 revealed in vivo
tumor formation, implying its growth-promoting and oncogenic property. We also showed that the expression of KIAA0101 was regulated tightly by the p53-p21 pathway. To consider the KIAA0101/
PCNA interaction as a therapeutic target, we designed the cell-permeable 20-amino-acid dominant-negative
peptide and found that it could effectively inhibit the KIAA0101/
PCNA interaction and resulted in the significant growth suppression of
cancer cells. Our results clearly implicated that suppression of the KIAA0101 and
PCNA oncogenic activity, or the inhibition of KIAA0101/
PCNA interaction, is likely to be a promising strategy to develop novel
cancer therapeutic drugs.