European Journal of Medical Research | |
Expressions of heparanase and upstream stimulatory factor in hepatocellular carcinoma | |
Min Zhong1  Wei Cui2  Ming-Shi Wu2  Xiao-Peng Chen2  Bin Chen2  | |
[1] Central Laboratory, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui Province, China;Department of General Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui Province, China | |
关键词: Recurrence; Hepatocellular carcinoma; Upstream stimulatory factor; Heparanase; | |
Others : 1107181 DOI : 10.1186/s40001-014-0045-9 |
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received in 2014-02-17, accepted in 2014-08-06, 发布年份 2014 |
【 摘 要 】
Background
The expression of heparanase (HPSE) was associated with postoperative metastatic recurrence in patients with hepatocellular carcinoma (HCC). The six E-box binding sites in the core promoter of the HPSE gene suggested that transcription factors of E-box such as upstream stimulatory factor (USF) might regulate the transcription of the HPSE gene. The aim of our study is to measure the levels of HPSE and USF expression and investigate the relationship between USF expression and clinicopathological parameters in patients with HCC.
Methods
HPSE, USF1 and USF2 expressions in human HCC cell lines (BEL-7402, HepG2 and HCCLM3) and 15 fresh human HCC tissue samples were measured by real-time reverse transcriptase-PCR and Western blot analysis. The normal liver cell line QSG7701 or fresh normal liver tissue samples obtained from 15 additional surgical patients with hepatic rupture was used as a control. The protein expressions were determined by immunohistochemistry in paraffin-embedded human HCC tissues and corresponding non-neoplastic tumor surrounding tissues (NTST) of 57 patients.
Results
HPSE, USF1 and USF2 mRNA expressions were increased in HCC cell lines and HCC tissues compared with normal liver cell line and normal liver tissue. The protein expressions of HPSE, USF1 and USF2 in HCC cell lines and HCC tissues were also increased. Both USF1 and USF2 expressions were positively correlated with HPSE. USF1 and USF2 expressions were increased in patients with liver cirrhosis, worse tissue differentiation, advanced HCC stages and metastatic recurrence.
Conclusions
Increased USF in HCC is associated with HPSE expression. USF might be an important factor in regulating HPSE expression and act as a novel marker of metastatic recurrence of HCC patients.
【 授权许可】
2014 Chen et al.
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【 参考文献 】
- [1]El-Serag HB: Hepatocellular carcinoma. New Engl J Med 2011, 365:1118-1127.
- [2]Aravalli RN, Steer CJ, Cressman EN: Molecular mechanisms of hepatocellular carcinoma. Hepatology 2008, 48:2047-2063.
- [3]El-Serag HB, Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterol 2007, 132:2557-2576.
- [4]Kussie PH, Hulmes JD, Ludwig DL, Patel S, Navarro EC, Seddon AP, Giorgio NA, Bohlen P: Cloning and functional expression of a human heparanase gene. Biochem Biophys Res Commun 1999, 261:183-187.
- [5]Vlodavsky I, Friedmann Y, Elkin M, Aingorn H, Atzmon R, Ishai-Michaeli R, Bitan M, Pappo O, Peretz T, Michal I, Spector L, Pecker I: Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med 1999, 5:793-802.
- [6]Toyoshima M, Nakajima M: Human heparanase. Purification, characterization, cloning and expression. J Biol Chem 1999, 274:24153-24160.
- [7]Chen XP, Liu YB, Rui J, Peng SY, Peng CH, Zhou ZY, Shi LH, Shen HW, Xu B: Heparanase mRNA expression and point mutation in hepatocellular carcinoma. World J Gastroenterol 2004, 10:2795-2799.
- [8]El-Assal ON, Yamanoi A, Ono T, Kohno H, Nagasue N: The clinicopathological significance of heparanase and basic fibroblast growth factor expressions in hepatocellular carcinoma. Clin Cancer Res 2001, 7:1299-1305.
- [9]Komatsu N, Waki M, Sue M, Tokuda C, Kasaoka T, Nakajima M, Higashi N, Irimura T: Heparanase expression in B16 melanoma cells and peripheral blood neutrophils before and after extravasation detected by novel anti-mouse heparanase monoclonal antibodies. J Immunol Methods 2008, 331:82-93.
- [10]Tang D, Zhang Q, Zhao S, Wang J, Lu K, Song Y, Zhao L, Kang X, Wang J, Xu S, Tian L: The expression and clinical significance of microRNA-1258 and heparanase in human breast cancer. Clin Biochem 2013, 46:926-932.
- [11]Xu YY, Zhang Y, Wang ZN, Xue Z, Li J, Yang L, Huimian X: Role of heparanase-1 in gastric carcinoma invasion. Asian Pac J Cancer Prev 2009, 10:151-154.
- [12]Jiang P, Kumar A, Parrillo JE, Dempsey LA, Platt JL, Prinz RA, Xu X: Cloning and characterization of the human heparanase-1 (HPR1) gene promoter. Role of GA-binding peotein and Sp1 in regulating HPR1 BASAL promoter activity. J Biol Chem 2002, 277:8989-8998.
- [13]DeMestre AM, Rao S, Hornby JR, Soe-Htwe T, Khachigian LM, Hulett MD: Early growth response gene 1 (EGR1) regulates heparanase gene transcription in tumor cells. J Biol Chem 2005, 280:35136-35147.
- [14]Rao G, Liu D, Xing M, Tauler J, Prinz RA, Xu X: Induction of heparanase-1 expression by mutant B-Raf kinase: role of GA binding protein in heparanase-1 promoter activation. Neoplasia 2010, 12:946-956.
- [15]Chen XP, Hu LH, Cui W, Wang D, Wu MS, Luo JS, Zhong M: Activity and tumor specificity of human heparanase gene core promoter. Mol Med Rep 2012, 6:867-871.
- [16]Sawadogo M: Multiple forms of the human gene-specific transcription factor USF. II. DNA binding properties and transcriptional activity of the purified HeLa USF. J Biol Chem 1988, 263:11994-12001.
- [17]Gregor PD, Sawadogo M, Roeder RG: The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev 1990, 4:1730-1740.
- [18]Sirito M, Walker S, Lin Q, Kozlowski MT, Klein WH, Sawadogo M: Members of the USF family of helix-loop-helix proteins bind DNA as homo- as well as heterodimers. Gene Expr 1992, 2:231-240.
- [19]Jung HS, Kim KS, Chung YJ, Chung HK, Min YK, Lee MS, Lee MK, Kim KW, Chung JH: USF inhibits cell proliferation through delay in G2/M phase in FRTL-5 cells. Endocr J 2007, 54:275-285.
- [20]Ocejo-Garcia M, Baokbah TA, Ashurst HL, Cowlishaw D, Soomro I, Coulson JM, Woll PJ: Roles for USF2 in lung cancer proliferation and bronchial carcinogenesis. J Pathol 2005, 206:151-159.
- [21]van Deursen D, van Leeuwen M, Vaulont S, Jansen H, Verhoeven AJ: Upstream stimulatory factors 1 and 2 activate the human hepatic lipase promoter via E-box dependent and independent mechanisms. Biochim Biophys Acta 2009, 1791:229-237.
- [22]Ismail PM, Lu T, Sawadogo M: Loss of USF transcriptional activity in breast cancer cell lines. Oncogene 1999, 18:5582-5591.
- [23]Yang BW, Liang Y, Xia JL, Sun HC, Wang L, Zhang JB, Tang ZY, Liu KD, Chen J, Xue Q, Chen J, Gao DM, Wu WZ: Biological characteristics of fluorescent protein-expressing human hepatocellular carcinoma xenograft model in nude mice. Eur J Gastroenterol Hepatol 2008, 20:1077-1084.