title: Identification of PFTAIRE protein kinase 1, a novel cell division cycle-2 related gene, in the motile phenotype of hepatocellular carcinoma cells.
abstract: 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.
authors.affiliation: Li Ka-Shing Institute of Health, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Etonia Y-T
authors.initials: EY
authors.lastname: Pang
authors.forename: Alfa H-C
authors.initials: AH
authors.lastname: Bai
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: To
authors.forename: Shirley M-H
authors.initials: SM
authors.lastname: Sy
authors.forename: Navy L-Y
authors.initials: NL
authors.lastname: Wong
authors.forename: Paul B-S
authors.initials: PB
authors.lastname: Lai
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wong
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D016203:CDC2 Protein Kinase; C515076:CDK14 protein, human; D018844:Cyclin-Dependent Kinases