title: Overexpression of E2F1 promotes tumor malignancy and correlates with TNM stages in clear cell renal cell carcinoma.
abstract: BACKGROUND
  Transcription factor E2F1 exerts effects on many types of cancers. As an upstream regulator of a host of genes, E2F1 can trigger diverse aberrant transcription processes that may dominate malignancy. Clear cell renal cell carcinoma (ccRCC) is the most common subtype in renal cell carcinoma which displays high malignancy and has a shortage of biomarkers in clinics. Our study aimed to explore the function of E2F1 in ccRCC and its correlation with clinicopathological parameters.
  
  
  RESULTS
  Transcription factor E2F1 was mainly distributed in cancer cell nucleus and mRNA expression signiﬁcantly increased in 72 cases of clear cell renal cell carcinoma (ccRCC) tissues compared with adjacent non-cancerous kidney tissues (p<0.001). The protein expression was consistent with mRNA expression. Further analysis in 92 cases indicated that E2F1 mRNA level expression was associated with the tumor pathologic parameters embracing diameter, Fuhrman tumor grade, pT stage, TNM stage grouping and macrovascular infiltration (MAVI). These surgical specimens had high grade tumors accompanied with an elevated E2F1 expression. Moreover, E2F1 transfection was found to contribute significantly to cancer cell proliferation, migration and invasion in vitro.
  
  
  CONCLUSIONS
  Overexpression of E2F1 may be a key event in the local and vascular infiltration of ccRCC indicated by the activation of matrix metalloproteinase (MMP) 2 and MMP9. These findings highlighted the implication of E2F1's function in the metastatic process. Furthermore, the clinical relevance of E2F1 in ccRCC pointed to a potential new therapeutic target.
authors.affiliation: Department of Urology/State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.forename: Dong
authors.initials: D
authors.lastname: Ni
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weihao
authors.initials: W
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Erlin
authors.initials: E
authors.lastname: Song
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Huang
authors.forename: Qing
authors.initials: Q
authors.lastname: Ai
authors.forename: Hongzhao
authors.initials: H
authors.lastname: Li
authors.forename: Baojun
authors.initials: B
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
authors.forename: Taoping
authors.initials: T
authors.lastname: Shi
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D063646:Carcinogenesis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D059748:Proteolysis; D012189:Retrospective Studies; D016196:S Phase / Q000235:genetics; D015854:Up-Regulation
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
references.citation: Oncogene. 2005 Mar 31;24(14):2375-85
references.pmid: 15674322
references.citation: Cancer Res. 2006 Dec 15;66(24):11897-906
references.pmid: 17178887
references.citation: Cancer Res. 2012 Feb 1;72(3):571-5
references.pmid: 22298593
references.citation: In Vitro. 1978 Sep;14(9):779-86
references.pmid: 721102
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: PLoS One. 2012;7(4):e35022
references.pmid: 22506064
references.citation: Cell. 1998 Aug 7;94(3):353-62
references.pmid: 9708737
references.citation: Cancer Lett. 2009 Apr 8;276(1):88-94
references.pmid: 19081179
references.citation: Genes Dev. 2001 Feb 1;15(3):267-85
references.pmid: 11159908
references.citation: Cell. 1985 Sep;42(2):469-77
references.pmid: 2411423
references.citation: Cancer Res. 2012 Jan 15;72(2):516-26
references.pmid: 22086850
references.citation: Tumour Biol. 2012 Feb;33(1):9-16
references.pmid: 22125026
references.citation: Nucleic Acids Res. 2006 Apr 14;34(7):2046-55
references.pmid: 16617145
references.citation: J Natl Cancer Inst. 2005 Nov 2;97(21):1589-600
references.pmid: 16264179
references.citation: J Urol. 2012 Feb;187(2):418-23
references.pmid: 22177164
references.citation: Am J Obstet Gynecol. 2011 May;204(5):411.e1-411.e11
references.pmid: 21316642
references.citation: J Clin Oncol. 2010 Jun 1;28(16):2660-7
references.pmid: 20421545
references.citation: Eur Urol. 2010 Sep;58(3):398-406
references.pmid: 20633979
references.citation: Ann Surg Oncol. 2010 Feb;17(2):564-71
references.pmid: 19841979
references.citation: Cancer Biol Ther. 2004 Apr;3(4):395-9
references.pmid: 14726656
references.citation: Korean J Pathol. 2012 Aug;46(4):341-8
references.pmid: 23110026
references.citation: J Natl Cancer Inst. 2010 Jan 20;102(2):127-33
references.pmid: 20026813
references.citation: J Clin Pathol. 2008 May;61(5):601-5
references.pmid: 17908803
references.citation: BMC Mol Biol. 2007 Jun 08;8:47
references.pmid: 17559644
references.citation: Anticancer Res. 2008 Jul-Aug;28(4B):2135-9
references.pmid: 18751386
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530
references.citation: Nature. 1993 Sep 23;365(6444):349-52
references.pmid: 8377827