Malignant transformation of 293 cells induced by ectopic expression of human Nanog.
Tumor development has long been known to resemble abnormal embryogenesis. The ESC self-renewal gene NANOG is purportedly expressed in some epithelial cancer cells and solid tumors, but a casual role in tumor development has remained unclear. In order to more comprehensively elucidate the relationship between human Nanog and tumorigenesis, the hNanog was ectopically expressed in the 293 cell line to investigate its potential for malignant transformation of cells both in vitro and in vivo. Here we provide compelling evidence that the overexpression of hNanog resulted in increased cell proliferation, anchor-independent growth in soft agar, and formation of tumors after subcutaneous injection of athymic nude mice. Pathologic analysis revealed that these tumors were poorly differentiated. In analysis of the underlying molecular mechanism, two proteins, FAK and Ezrin, were identified to be upregulated in the hNanog expressing 293 cells. Our results demonstrate that hNanog is a potent human oncogene and has the ability to induce cellular transformation of human cells.
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongdajie Street, Fengtai, Beijing 100071, People's Republic of China.
Yan-Li
YL
Lin
Zheng-Bin
ZB
Han
Fu-Yin
FY
Xiong
Li-Yuan
LY
Tian
Xiao-Jie
XJ
Wu
Shi-Wei
SW
Xue
Yan-Rong
YR
Zhou
Ji-Xian
JX
Deng
Hong-Xing
HX
Chen
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D000071317:Nanog Homeobox Protein; D009857:Oncogenes; D015854:Up-Regulation; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; D000099149:Ezrin; C486780:NANOG protein, human
J Proteome Res. 2008 Apr;7(4):1458-69
18257521
Nature. 1994 Dec 22-29;372(6508):786-91
7997267
Stem Cells. 2009 May;27(5):993-1005
19415763
Cell. 2005 Sep 23;122(6):947-56
16153702
Cancer Res. 1995 Jul 1;55(13):2752-5
7796399
Int J Cancer. 1996 Oct 9;68(2):164-71
8900422
J Cell Biol. 1996 Dec;135(5):1383-90
8947559
J Cell Biol. 1992 Nov;119(4):893-903
1385444
Cancer. 2005 Nov 15;104(10):2092-8
16206293
Cancer Cell. 2004 Dec;6(6):625-30
15607966
J Cell Biol. 1996 Aug;134(3):793-9
8707856
Curr Opin Oncol. 2003 Jan;15(1):44-9
12490760
J Biol Chem. 1992 Nov 25;267(33):23439-42
1429685
Cell. 2003 May 30;113(5):643-55
12787505
Nat Rev Cancer. 2002 Oct;2(10):777-85
12360280
Nat Med. 2004 Feb;10(2):182-6
14704791
Oncogene. 1997 Jul 17;15(3):265-74
9233761
Cancer Lett. 2008 Mar 8;261(1):55-63
18155831
Biochem Biophys Res Commun. 2005 Dec 16;338(2):1098-102
16259959
Cancer Res. 2008 Jun 1;68(11):4311-20
18519691
Oncogene. 2005 Sep 8;24(40):6174-84
15940260
Cancer Res. 2004 Jul 1;64(13):4577-84
15231669
FASEB J. 2008 Oct;22(10):3696-705
18614581
Cancer. 2005 Nov 15;104(10):2255-65
16228988
Am J Pathol. 2008 Oct;173(4):1165-72
18772339
Lancet. 1993 Oct 23;342(8878):1024-5
8105266
Mol Cell Proteomics. 2007 Feb;6(2):294-304
17110434
Cell. 2003 May 30;113(5):631-42
12787504
Mol Biol Cell. 2007 May;18(5):1543-53
17314394
J Invest Dermatol. 1995 Jul;105(1):104-8
7615962
Clin Cancer Res. 2000 Jun;6(6):2417-23
10873094
Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192-6
1594631
BMC Cancer. 2008 Apr 18;8:108
18419830
Stem Cells Dev. 2009 Sep;18(7):1013-22
19102659
Nature. 2001 Nov 1;414(6859):105-11
11689955
Nat Genet. 2008 May;40(5):499-507
18443585
Clin Cancer Res. 2008 Jul 1;14(13):4085-95
18593985
Int J Biochem Cell Biol. 1997 Aug-Sep;29(8-9):1085-96
9416004