Expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in neuroblastoma: correlation with clinical features, cellular localization, and cerulenin-mediated apoptosis regulation.
OBJECTIVE
Prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is a novel 19-kDa protein that has recently been implicated in human cancer. In the present study, we analyzed for the first time PRAF2 mRNA expression in a large set of human tumors. The high expression in neuroblastic tumors prompted us to analyze PRAF2 expression correlations with genetic and clinical features of these tumors. In addition, we determined the localization of PRAF2 protein in neuroblastoma cells and studied its regulation in apoptosis.


METHODS
Affymetrix microarray analysis was done with a set of 41 different tumor types (1,426 samples) in the public domain, a set of three different neuroblastic tumor types (110 samples), and a panel of 25 neuroblastoma cell lines. The subcellular localization of endogenous PRAF2 in neuroblastoma cells was identified by immunofluorescence microscopy and apoptosis detected by Annexin V staining and poly(ADP-ribose) polymerase cleavage.


RESULTS
PRAF2 mRNA was detected in 970 of 1,426 samples in the public data set. All 110 neuroblastic tumors expressed PRAF2 at higher levels than any other tumor examined. Importantly, PRAF2 expression levels significantly correlated with the following clinical features: patient age at diagnosis (P = 6.19 x 10(-5)), survival (P = 1.32 x 10(-3)), International Neuroblastoma Staging System stage (P = 2.86 x 10(-4)), and MYCN amplification (P = 3.74 x 10(-3)). PRAF2 localized in bright cytoplasmic punctae and protein levels increased in neuroblastoma cells that underwent cerulenin-induced apoptosis.


CONCLUSIONS
Elevated PRAF2 expression levels correlated with unfavorable genetic and clinical features, suggesting PRAF2 as a candidate prognostic marker of neuroblastoma.
Geerts
Dirk
D
Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Wallick
Christopher J
CJ
Koomoa
Dana-Lynn T
DL
Koster
Jan
J
Versteeg
Rogier
R
Go
Ramon Christopher V
RC
Bachmann
André S
AS
D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002569:Cerulenin / Q000378:metabolism*; D002675:Child, Preschool; D011992:Endosomes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017434:Protein Structure, Tertiary; D014018:Tissue Distribution
D002352:Carrier Proteins; D008565:Membrane Proteins; C499863:PRAF2 protein, human; D002569:Cerulenin