Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer.
CD147 is a novel cancer-associated biomarker that plays an important role in the invasion and metastasis of human lung cancer. In spite of its many known functions, little is known about CD147 transcriptional regulation. In this study, we explored the regulation of CD147 in human lung cancer tissues. Over 60% of the human lung cancer tissues expressed differential high levels of CD147. We then cloned the 5'-flanking region of the human CD147 gene and identified a critical promoter region at -108 to -42 which contained one binding site for Sp1, which was essential in up-regulating CD147 promoter activity. These results were proven by blocking Sp1 using RNAi or mithramycin A treatment and up-regulating Sp1 using transfection with eukaryotic expression vector. Consistent with the CD147 transcription activation, a high level of Sp1 expression was detected in lung cancer cell lines overexpressing CD147. Chromatin immunoprecipitation assay showed that much more Sp1 could bind to the CD147 promoter in 95-D with CD147 high expression than in SK-MES-1 with CD147 low expression. There was a significant positive correlation between CD147 expression and Sp1 expression level detected by immunohistochemistry (r = 0.831). Collectively, our results suggest that Sp1 is essential for regulating the CD147 gene expression in human lung cancer.
Kong
Ling-Min
LM
Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
Liao
Cheng-Gong
CG
Fei
Fei
F
Guo
Xu
X
Xing
Jin-Liang
JL
Chen
Zhi-Nan
ZN
D051926:Basigin / Q000032:analysis / Q000235:genetics*; D001665:Binding Sites; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D016329:Sp1 Transcription Factor / Q000502:physiology*
C497886:BSG protein, human; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D051926:Basigin
Arch Biochem Biophys. 1991 Feb 15;285(1):90-6
1846736
Cell. 1983 Mar;32(3):669-80
6187469
Cancer Res. 2001 May 15;61(10):4143-54
11358838
FEBS Lett. 2005 May 23;579(13):2811-6
15907486
Biochem J. 2005 Nov 15;392(Pt 1):1-11
16266294
Mol Cancer Res. 2007 Jun;5(6):605-14
17579119
Gene. 1999 Oct 1;238(2):291-300
10570957
Histopathology. 2009 May;54(6):677-87
19438743
Circ Res. 2003 Dec 12;93(12):1202-9
14593001
Cell. 1983 Nov;35(1):79-87
6313230
Cancer Res. 1989 Jun 15;49(12):3385-91
2541902
Physiol Rev. 2007 Jan;87(1):69-98
17237343
Oncology. 2007;72(3-4):197-204
18160808
Eur J Cancer. 2005 Nov;41(16):2438-48
16209919
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4273-8
9113979
Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):4109-17
15217947
CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
19474385
World J Gastroenterol. 2003 Oct;9(10):2174-7
14562372
J Cell Physiol. 2001 Aug;188(2):143-60
11424081
J Biol Chem. 2001 Mar 9;276(10):7549-58
11114309
Gene. 1998 Oct 5;220(1-2):99-108
9767135
Mod Pathol. 2008 Sep;21(9):1130-8
18567995
Cancer Res. 2000 Feb 15;60(4):888-91
10706100
Methods. 2001 Dec;25(4):402-8
11846609
Cancer Res. 1993 Jul 1;53(13):3154-8
8319225
Gene. 2002 Jan 9;282(1-2):75-86
11814679
Cell. 1997 May 16;89(4):619-28
9160753
Cancer Res. 1995 Jan 15;55(2):434-9
7812975
J Biol Chem. 1993 May 5;268(13):9296-301
8486625
Zhonghua Zhong Liu Za Zhi. 1992 Jan;14(1):9-12
1327694
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1488-94
16574895
J Biol Chem. 2001 Dec 14;276(50):46870-7
11591720
Am J Pathol. 2001 Jun;158(6):1921-8
11395366
Blood. 2002 Nov 1;100(9):3325-32
12384434