Subcellular distribution and expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in malignant glioma: Influence on cell survival and migration.
Our previous studies revealed that the expression of the 19-kDa protein prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is elevated in cancer tissues of the breast, colon, lung, and ovary, when compared to noncancerous tissues of paired samples. PRAF2 mRNA expression also correlated with several genetic and clinical features and is a candidate prognostic marker in the pediatric cancer neuroblastoma. The PRAF2-related proteins, PRAF1 and PRAF3, play multiple roles in cellular processes, including endo/exocytic vesicle trafficking and glutamate uptake. PRAF2 shares a high sequence homology with these family members, but its function remains unknown. In this study, we examined PRAF2 mRNA and protein expression in 20 different human cancer types using Affymetrix microarray and human tissue microarray (TMA) analyses, respectively. In addition, we investigated the subcellular distribution of PRAF2 by immunofluorescence microscopy and cell fractionation studies. PRAF2 mRNA and protein expression was elevated in several cancer tissues with highest levels in malignant glioma. At the molecular level, we detected native PRAF2 in small, vesicle-like structures throughout the cytoplasm as well as in and around cell nuclei of U-87 malignant glioma cells. We further found that monomeric and dimeric forms of PRAF2 are associated with different cell compartments, suggesting possible functional differences. Importantly, PRAF2 down-regulation by RNA interference significantly reduced the cell viability, migration, and invasiveness of U-87 cells. This study shows that PRAF2 expression is elevated in various tumors with exceptionally high expression in malignant gliomas, and PRAF2 therefore presents a candidate molecular target for therapeutic intervention.
Borsics
Tamás
T
Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
Lundberg
Emma
E
Geerts
Dirk
D
Koomoa
Dana-Lynn T
DL
Koster
Jan
J
Wester
Kenneth
K
Bachmann
André S
AS
D000595:Amino Acid Sequence; D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009837:Oligodendroglioma / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D017368:Protein Prenylation; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D008565:Membrane Proteins; C499863:PRAF2 protein, human; D012333:RNA, Messenger
J Toxicol Environ Health A. 2007 Jun;70(11):876-84
17479401
J Biol Chem. 2001 Jul 20;276(29):27354-62
11373297
Biochem Biophys Res Commun. 2000 Aug 28;275(2):509-16
10964695
Nature. 2001 Mar 1;410(6824):84-8
11242046
Proteomics. 2007 Jun;7(13):2142-50
17549799
J Proteomics. 2008 Oct 7;71(4):448-60
18656560
Blood. 1998 Jun 1;91(11):4282-91
9596677
J Neurooncol. 2004 Dec;70(3):301-7
15662971
Nature. 2001 Mar 1;410(6824):50-6
11242036
Neuroreport. 2002 Nov 15;13(16):2079-84
12438930
Gene. 2006 Apr 12;371(1):154-65
16481131
Biochem Biophys Res Commun. 2006 Oct 13;349(1):200-8
16930546
Nature. 2003 Oct 23;425(6960):856-9
14574414
Neoplasia. 2007 Jan;9(1):36-46
17325742
Cancer Cell. 2006 May;9(5):391-403
16697959
J Biol Chem. 2001 Jul 27;276(30):28219-25
11335720
J Neurosci. 2008 Sep 17;28(38):9404-13
18799673
Biochem J. 2004 May 15;380(Pt 1):43-9
14979871
Exp Cell Res. 2008 Feb 15;314(4):707-19
18201699
Mol Cell Proteomics. 2005 Dec;4(12):1920-32
16127175
Biochem Biophys Res Commun. 1999 May 19;258(3):657-62
10329441
Clin Exp Pharmacol Physiol. 2006 Sep;33(9):816-24
16922813
Cell Signal. 2007 Jun;19(6):1315-27
17336041
FEBS Lett. 2005 Mar 14;579(7):1751-8
15757671
Mol Cancer Ther. 2009 Jul;8(7):2067-75
19584241
EMBO J. 2006 Sep 6;25(17):4120-30
16917502
Cell Signal. 2009 Dec;21(12):1901-9
19733236
J Biol Chem. 2008 Nov 14;283(46):31323-32
18684713
J Biol Chem. 2001 Mar 2;276(9):6225-33
11096102
Nucleic Acids Res. 2009 Jan;37(Database issue):D885-90
18940857
Cancer Res. 2003 Aug 1;63(15):4724-30
12907655
J Cell Mol Med. 2009 Jan;13(1):114-24
18363836
Genes Dev. 2001 Jun 1;15(11):1311-33
11390353
J Clin Oncol. 2003 Apr 15;21(8):1624-36
12697889
Proteomics. 2005 Nov;5(17):4327-37
16237735
J Histochem Cytochem. 2006 Dec;54(12):1413-23
16957166
Gene. 2006 Apr 12;371(1):144-53
16472945
Genome Biol. 2006;7 Suppl 1:S12.1-14
16925834
Biochem Cell Biol. 2006 Dec;84(6):940-8
17215881
J Biol Chem. 2000 Jun 16;275(24):18511-9
10751420
Clin Cancer Res. 2007 Nov 1;13(21):6312-9
17975142
PLoS One. 2007 Oct 10;2(10):e1016
17925864
Cancer Cell. 2006 Apr;9(4):287-300
16616334
J Biol Chem. 2008 Mar 7;283(10):6175-83
18167356
N Engl J Med. 2005 Mar 10;352(10):987-96
15758009
Clin Biochem. 2004 Jul;37(7):584-94
15234240
Neurosci Lett. 2008 May 9;436(2):171-6
18395978