Identification of PFTAIRE protein kinase 1, a novel cell division cycle-2 related gene, in the motile phenotype of hepatocellular carcinoma cells.
Metastasis is a major cause of cancer morbidity and mortality in individuals with hepatocellular carcinoma (HCC), yet little is known about the underlying molecular basis. Using genetic information derived from chromosome-based comparative genomic hybridization, we have reported previously on regional chromosome 7q21-q22 gains in close association with HCC progression. In this study, we undertook cDNA microarray-based comparative genomic hybridization, to examine the 7q21-q22 region for the involved gene(s) in HCC. High-resolution mapping analysis highlighted 7 candidates, namely PFTAIRE protein kinase 1 (PFTK1), ODAG, CDK6, CAS1, PEX1, SLC25A, and PEG10, within the region. Quantitative reverse transcription (RT)-PCR evaluation further indicated upregulation of a single candidate gene, PFTK1, that correlated significantly with both advanced metastatic HCCs (P = 0.032) and tumor microvascular invasion (P = 0.012). Given that little is known about the function(s) of PFTK1, which is a novel cell division cycle (Cdc)2-related gene, we examined its potential role in the motile phenotype of HCC cells by both ectopic expression and knockdown investigations. RNA-interference knockdown of PFTK1 in invasive Hep3B cells resulted in a significant reduction in cell invasion, chemotactic migration, and cell motility (P < 0.001). Conversely, ectopic expression of PFTK1 in noninvasive HKCI-C3 cells induced substantial cellular invasion and migration (P < or = 0.007). In neither cell line was there any effect on cell viability. Immunofluorescence showed marked filamentous actin polymerizations in PFTK1-expressing cells.


CONCLUSIONS
In this study, we have thus provided preliminary evidence that overexpression of PFTK1 may confer a motile phenotype in malignant hepatocytes that accounts for the association of upregulation of this gene in metastatic HCC.
Pang
Etonia Y-T
EY
Li Ka-Shing Institute of Health, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Bai
Alfa H-C
AH
To
Ka-Fai
KF
Sy
Shirley M-H
SM
Wong
Navy L-Y
NL
Lai
Paul B-S
PB
Squire
Jeremy A
JA
Wong
Nathalie
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016203:CDC2 Protein Kinase / Q000032:analysis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D018844:Cyclin-Dependent Kinases; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D016203:CDC2 Protein Kinase; C515076:CDK14 protein, human; D018844:Cyclin-Dependent Kinases