HLJ1在肝细胞癌组织中的表达及生物学意义
摘要
肝细胞癌(Hepatocellular carcinoma,HCC)是常见的恶性肿瘤之一,具有高度的侵袭转移能力。HCC复发转移是导致大多数HCC病人术后复发率高,预后差的主要原因。肝癌细胞的增殖、运动是肝癌侵袭转移的关键性步骤。HLJ1(DnaJ-like heat shock protein)是最新发现的DnaJ-like Hsp40家族成员之一,研究表明,HLJ1参与了STAT1和P21~(WAF1)信号路径,有抑制细胞生长、增殖、迁移等功能。HLJ1能增加P21~(WAF1)的表达,并且不依赖于P53途径,降低cyclin D1的表达;P21~(WAF1)的表达上调和Cyclin D1的表达下调能够减缓细胞分裂和肿瘤细胞的生长。此外,HLJ1能上调钙粘蛋白E的表达,从而降低细胞的侵袭力。本研究中,我们首次研究了HLJ1在肝癌组织中的表达情况,并通过和临床病理特征的分析,探讨其表达的生物学意义。
目的:研究HLJ1在肝癌组织中的表达情况,并通过和临床病理特征的分析,探讨其表达的生物学意义。
方法:32例HCC及其对应的癌旁组织标本均取自中南大学湘雅医院外科。所有标本均经病理组织学检查确诊。采用逆转录聚合酶链反应(RT-PCR),检测了32例肝癌组织及其对应的癌旁组织中的HLJ1基因的mRNA表达水平。并分析HLJ1与HCC的肝硬化、结节数目、静脉浸润、分化程度和肝外转移等临床病理特征的关系。
结果:RT-PCR结果显示HCC组织中HLJ1 mRNA的表达水平显著性低于对应的癌旁组织(1.18±0.82 vs 1.92±1.15,P＜0.05)。HLJ1mRNA低表达组(n_1=18)和高表达组(n_2=14)在静脉浸润(P=0.001)和细胞分化程度(P=0.010)方面的差异具有显著意义,而在性别、肝硬化、肿瘤直径和结节数目方面无显著性差异。
结论:与癌旁组织相比,HLJ1在HCC中表达显著性下调。HLJ1可能参与了肝癌的细胞分化和侵袭转移。
Hepatocellular carcinoma is a common malignant tumor with higher invasion and metastastic potential,which lead to a poor prognosis of major patients and a high recurrence post operation.Proliferation and migration of cancer cell are the key steps for hepatocellular invasion and metastasis.HLJ1 is a new member of DnaJ-like heat shock protein 40 family.Previous studies have revealed that HLJ1 could regulate cell proliferation and migration.HLJ1 can inhibit cell devision and proliferation by up-regulating P21~(WAF1)and down-regulating Cyclin D in a P53-independent manner.Furthermore,HLJ1 can inhibit cell migration by up-regulating cadherin E.In this research,we detected the expression levels of HLJ1 in the tissue of HCC for the first time,and analyzed the relationship between the HLJ1 expression levels and the clinicopathological characteristics of HCC.
Objective:To analyze the expression of HLJ1 in the tissues of hepatocellular carcinoma(HCC)and the correlation between its expression and clinical pathological characteristic.
Methods:HLJ1 mRNA expression level was determined in 32 HCC tissues and their paracarcinomatous liver tissues(PCLT)by reverse transcription polymerase chain reaction(RT-PCR).The correlation of HLJ1 expression level with clinicopathologic variables was also analyzed.
Results:HLJ1 mRNA expression level was significantly lower in HCC than in PCLT(1.18±0.82 vs 1.92±1.15,P＜0.05).Importantly, the HLJ1 mRNA expression level correlated with the Edmondson-Steiner grade(P=0.010)and vein invasion(P=0.001).
Conclusion:Our study indicates that HLJ1 mRNA expression level in HCC tissues is significantly lower than that in PCLT.HLJ1 may participate in the cell proliferation and migration of HCC cell.
目的:研究HLJ1在肝癌组织中的表达情况,并通过和临床病理特征的分析,探讨其表达的生物学意义。
方法:32例HCC及其对应的癌旁组织标本均取自中南大学湘雅医院外科。所有标本均经病理组织学检查确诊。采用逆转录聚合酶链反应(RT-PCR),检测了32例肝癌组织及其对应的癌旁组织中的HLJ1基因的mRNA表达水平。并分析HLJ1与HCC的肝硬化、结节数目、静脉浸润、分化程度和肝外转移等临床病理特征的关系。
结果:RT-PCR结果显示HCC组织中HLJ1 mRNA的表达水平显著性低于对应的癌旁组织(1.18±0.82 vs 1.92±1.15,P＜0.05)。HLJ1mRNA低表达组(n_1=18)和高表达组(n_2=14)在静脉浸润(P=0.001)和细胞分化程度(P=0.010)方面的差异具有显著意义,而在性别、肝硬化、肿瘤直径和结节数目方面无显著性差异。
结论:与癌旁组织相比,HLJ1在HCC中表达显著性下调。HLJ1可能参与了肝癌的细胞分化和侵袭转移。
Hepatocellular carcinoma is a common malignant tumor with higher invasion and metastastic potential,which lead to a poor prognosis of major patients and a high recurrence post operation.Proliferation and migration of cancer cell are the key steps for hepatocellular invasion and metastasis.HLJ1 is a new member of DnaJ-like heat shock protein 40 family.Previous studies have revealed that HLJ1 could regulate cell proliferation and migration.HLJ1 can inhibit cell devision and proliferation by up-regulating P21~(WAF1)and down-regulating Cyclin D in a P53-independent manner.Furthermore,HLJ1 can inhibit cell migration by up-regulating cadherin E.In this research,we detected the expression levels of HLJ1 in the tissue of HCC for the first time,and analyzed the relationship between the HLJ1 expression levels and the clinicopathological characteristics of HCC.
Objective:To analyze the expression of HLJ1 in the tissues of hepatocellular carcinoma(HCC)and the correlation between its expression and clinical pathological characteristic.
Methods:HLJ1 mRNA expression level was determined in 32 HCC tissues and their paracarcinomatous liver tissues(PCLT)by reverse transcription polymerase chain reaction(RT-PCR).The correlation of HLJ1 expression level with clinicopathologic variables was also analyzed.
Results:HLJ1 mRNA expression level was significantly lower in HCC than in PCLT(1.18±0.82 vs 1.92±1.15,P＜0.05).Importantly, the HLJ1 mRNA expression level correlated with the Edmondson-Steiner grade(P=0.010)and vein invasion(P=0.001).
Conclusion:Our study indicates that HLJ1 mRNA expression level in HCC tissues is significantly lower than that in PCLT.HLJ1 may participate in the cell proliferation and migration of HCC cell.
引文
[1]Akriviadis EA,Llovet JM,Efrenmidis SC,et al.Hepatocellular carcinoma Br J Surg.1998,85(10):1319-1331.
[2]张思维,李连弟,鲁凤珠,等.中国1990-1992年原发性肝癌死亡调查分析.中华肿瘤杂志.1999,21:245-249.
[3]Marrero JA.Hepatocellular Carcinoma.Curr Opinion Gastroenterology.2004,20(3):248-253.
[4]Lee GJ,Vierling E.A small heat shock protein cooperates with heat shock protein 70 systems to reactivate a heat-denatured protein.Plant Physiol,2000,122(1):189-198.
[5]Zatloukal K,Stumptner C,Fuchsbichler A,et al.p62 is a common component of cytoplasmic inclusions in protein aggregation diseases.Am J Pathol,2002,160(1):255-263.
[6]Park HS,Lee JS,Huh SH,et al.Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase.EMBO J,2001,20(3):446-456.
[7]Kasi VS,Kuppuswamy D.Inhibition of src family kinase by a combinatorial action of 5-AMP and small heat shock proteins identified from the adult heat.Mol Cell Biol,1999,19(10):6858-6871.
[8]Stangl K,Gunther C,Frank T,et al.Inhibition of the Ublquitln-Proteasome Pathway Induces Differential Heat-Shoek Protein Response in Cardiomyocytes and Renders Early Cardiac Protection.BiochemBiophys Res Commun,2002,291(1):542-549.
[9]Lu AL,Xu CS.Effects of heat shock on change of HSC70/HSP68 acid and alkaline phosphatases before and after rat partial hepatectomy.World J Gastroenterol,2000,6(5):730-733.
[10]Hoe KL,Won M,Chung KS,et al.Isolation of a new member of DnaJ-like heat shock protein 40(Hsp40)from human liver.Biochimica et Biophysica Acta,1998,1383(1):4-8.
[11]Wang CC,Tsai MF.The transcriptional factor YY1 upregulates the novel invasion suppessor HLJ1 expression and inhibits cancer cell invasion.Oncogene,2005,24(25):4081-4093.
[12]Tsai MF,Wang CC,Chang GC,et al.A New Tumor Suppressor DnaJ-like Heat Shock Protein,HLJ1,and Survival of Patients With Non-Small Cell Lung Carcinoma.Journal of the National Cancer Institute,2006,98(12):825-838.
[13]Yang ZY,Perkins ND,Ohno T,et al.The p21 cyclin dependent kinase inhibitor suppresses tumorigenicity in vivo.Nat Med,1995,1(10):1052-6
[14]Kumar A,Commane M,Flickinger TW,et al.Defective TNF-alpha-induced apoptosis in STATI-null cells due to low constitutive levels of caspases.Science,1997,278(5343):1630-2.
[15]Yu H,Jove R.The STATs of cancer--new molecular targets come of age.Nat Rev Cancer,2004,4(2):97-105.
[16]Stephanou A,Latchman DS.STAT-1:a novel regulator of apoptosis.Int J Exp Pathol,2003,84(6):239-44.
[17]Baldin V,Lukas J,Marcote MJ,Pagano M,Draetta G..Cyclin D1 is a nuclear protein required for cell cycle progression in G1.Genes Dev 1993,7(5):812-21.
[18]Bremnes RM,Veve R,Hirsch FR,et al.The E-cadherin cell-cell adhesion complex and lung cancer invasion,metastasis,and prognosis.Lung Cancer,2002,36(2):115-124.
[19]Bukholm IK,Nesland JM,Karesen R,et al.E-cadherin and alpha-,beta-,and gamma-catenin protein expression in relation to metastasis in human breast carcinoma.Pathol,1998,185(3):262-266.
[20]JW Chen,Konan Peck,Tse-Ming Hong,et al.Global Analysis of Gene Expression in Invasion by a Lung Cancer Model.Cancer research,2001,61(12):5223-5230.
[21]Edmondson HA,Steiner PE.Primery carcinoma of the liver:a study of 100 case among 48.900 necropsies.Cancer.1954,7(3):462-504.
[22]Tsal MF,Wang CC,Chang GC,et al.A New Tumor Suppressor DnaJ-like Heat Shock Protein,HLJ1,and Survival of Patients With Non - Small-Cell Lung Carcinoma[J].Journal of the National Cancer Institute,2006,98(12):825-838.
[23]Wang CC,Tsai MF.The transcriptional factor YY1 upregulates the novel invasion suppessor HLJ1 expression and inhibits cancer cell invasion.Oncogene,2005,24(25):4081-4093.
[24]Poon RT,Fan ST,et al.Different risk factors and prognosis for early and the late intrahepatic recurrence after resection of hepatocellular carcinama.Cancer, 2000,89(3):500-507.
[25] Shimada K,Sano T,Sakamoto Y,et al.A long-term follow-up and management study of hepatocellular carcinama patients surviving for 10 years or longer after curative hepatectomy.Cancer,2005,104(9):39-47
[26] Kaibori M, Matsui Y, Saito T, et al. Risk factors for different patterns of recurrence after resection of hepatocellular carcinoma. Anticancer Res. 2007; 27(4):2809-16.
[27] Shimada K, Sakamoto Y, Esaki M, et al. Analysis of prognostic factors affecting survival after initial recurrence and treatment efficacy for recurrence in patients undergoing potentially curative hepatectomy for hepatocellular carcinoma. Ann Surg Oncol. 2007;14(8):2337-47.
[28] Shimozawa N, Hanazaki K. Longterm prognosis after hepatic resection for small hepatocellular carcinoma. J Am Coll Surg. 2004;198(3):356-65.
[29] Yamada H, Kondo S, Okushiba S, et al. Analysis of predictive factors for recurrence after hepatectomy for colorectal liver metastases. World J Surg. 2001 ;25(9): 1129-33.
[30] Gruenberger T, Jourdan JL, Zhao J, et al. Echogenicity of liver metastases is an independent prognostic factor after potentially curative treatment. Arch Surg. 2000;135(11):1285-90.
[1]Lee GJ,Vierling E.A small heat shock protein cooperates with heat shock protein 70 systems to reactivate a heat-denatured protein.Plant Physiol,2000,122(1):189-198.
[2]Zatloukal K,Stumptner C,Fuchsbichler A,et al.p62 is a common component of cytoplasmic inclusions in protein aggregation diseases.Am J Pathol,2002,160(1):255-263.
[3]Park HS,Lee JS,Huh SH,et al.Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase.EMBO J,2001,20(3):446-456.
[4]Kasi VS,Kuppuswamy D.Inhibition of src family kinase by a combinatorial action of 5-AMP and small heat shock proteins identified from the adult heat.Mol Cell Biol,1999,19(10):6858-6871.
[5]Stangl K,Gunther C,Frank T,et al.Inhibition of the Ublquitln-Proteasome Pathway Induces Differential Heat-Shoek Protein Response in Cardiomyocytes and Renders Early Cardiac Protection.BiochemBiophys Res Commun,2002,291(3):542-549.
[6]Lu AL,Xu CS.Effects of heat shock on change of HSC70/HSP68 acid and alkaline phosphatases before and after rat partial hepatectomy.World J Gastroenterol,2000,6(5):730-733.
[7]Tsai MF,Wang CC,Chang GC,et al.A New Tumor Suppressor DnaJ-like Heat Shock Protein,HLJ1,and Survival of Patients With Non-Small Cell Lung Carcinoma.Journal of the National Cancer Institute,2006,98(12):825-838.
[8]Hoe KL,Won M,Chung KS,et al.Isolation of a new member of DnaJ-like heat shock protein 40(Hsp40)from human liver.Biochimica et Biophysica Acta, 1998,1383(1):4-8.
[9] Wang CC, Tsai MR The transcriptional factor YY1 upregulates the novel invasion suppessor HLJ1 expression and inhibits cancer cell invasion. Oncogene, 2005,24(25):4081-4093.
[10] Hattori H, Liu YC, Tohnai I, et al. Intracellular localization and partial amino acid sequence of a stress-inducible 40kDa protein in HeLa cells. Cell Struct. Funct. 1992,17(1 ):77 - 86.
[11] Ohtsuka K. Cloning of a cDNA for heat-shock protein hsp40 a human homologue of bacterial DnaJ. Res Commun. 1993,197(1):235 - 240.
[12] Qian YQ, Patel D, Hartl FU, et al. Nuclear magnetic resonance solution structure of the human Hsp40 (HDJ-1) J-domain. Mol Biol, 1996, 260(2): 224-35.
[13] Freeman BC, Myers MP, Schumacher R, et al. Identification of a regulatory motif in Hsp70 that affects ATPase activity, substrate binding and interaction with HDJ-1. EMBO J, 1995,14(10):2281-2292.
[14] Frydman J, Nimmesgern E, Ohtsuka, K, et al. Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature, 1994,370(6485): 111-117.
[15] Agarraberes FA, Dice JF. A molecular chaperone complex at the lysosomal membrane is required for protein translocation. Cell Sci, 2001,114(13):2491 - 2499.
[16] Fliss AE, Rao J, Melville MW, et al. Domain requirements of DnaJ-like (Hsp40) molecular chaperones in the activation of a steroid hormone receptor. Biol Chem, 1999,274(48):34045 - 34052.
[17] Hernandez MP, Chadli A, Tof DO. HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor. Biol Chem, 2002, 277(11):873 - 11881.
[18] Yang ZY, Perkins ND, Ohno T, et al. The p21 cyclin dependent kinase inhibitor suppresses tumorigenicity in vivo. Nat Med, 1995,1(10):1052 - 6.
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[20] Yu H, Jove R. The STATs of cancer—new molecular targets come of age. Nat Rev Cancer, 2004,4(2):97-105.
[21] Stephanou A, Latchman DS. STAT-1: a novel regulator of apoptosis. Int J Exp Pathol, 2003, 84(6):239-44.
[22] Baldin V, Lukas J, Marcote MJ, Pagano M, Draetta G. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev 1993, 7(5):812-21.
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[26] Bremnes RM, Veve R, Hirsch FR, et al. The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis, and prognosis. Lung Cancer, 2002, 36(2): 115- 124.
[27] Bukholm IK, Nesland JM, Karesen R, et al. E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. Pathol, 1998, 185(3): 262 - 266.
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[2]张思维,李连弟,鲁凤珠,等.中国1990-1992年原发性肝癌死亡调查分析.中华肿瘤杂志.1999,21:245-249.
[3]Marrero JA.Hepatocellular Carcinoma.Curr Opinion Gastroenterology.2004,20(3):248-253.
[4]Lee GJ,Vierling E.A small heat shock protein cooperates with heat shock protein 70 systems to reactivate a heat-denatured protein.Plant Physiol,2000,122(1):189-198.
[5]Zatloukal K,Stumptner C,Fuchsbichler A,et al.p62 is a common component of cytoplasmic inclusions in protein aggregation diseases.Am J Pathol,2002,160(1):255-263.
[6]Park HS,Lee JS,Huh SH,et al.Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase.EMBO J,2001,20(3):446-456.
[7]Kasi VS,Kuppuswamy D.Inhibition of src family kinase by a combinatorial action of 5-AMP and small heat shock proteins identified from the adult heat.Mol Cell Biol,1999,19(10):6858-6871.
[8]Stangl K,Gunther C,Frank T,et al.Inhibition of the Ublquitln-Proteasome Pathway Induces Differential Heat-Shoek Protein Response in Cardiomyocytes and Renders Early Cardiac Protection.BiochemBiophys Res Commun,2002,291(1):542-549.
[9]Lu AL,Xu CS.Effects of heat shock on change of HSC70/HSP68 acid and alkaline phosphatases before and after rat partial hepatectomy.World J Gastroenterol,2000,6(5):730-733.
[10]Hoe KL,Won M,Chung KS,et al.Isolation of a new member of DnaJ-like heat shock protein 40(Hsp40)from human liver.Biochimica et Biophysica Acta,1998,1383(1):4-8.
[11]Wang CC,Tsai MF.The transcriptional factor YY1 upregulates the novel invasion suppessor HLJ1 expression and inhibits cancer cell invasion.Oncogene,2005,24(25):4081-4093.
[12]Tsai MF,Wang CC,Chang GC,et al.A New Tumor Suppressor DnaJ-like Heat Shock Protein,HLJ1,and Survival of Patients With Non-Small Cell Lung Carcinoma.Journal of the National Cancer Institute,2006,98(12):825-838.
[13]Yang ZY,Perkins ND,Ohno T,et al.The p21 cyclin dependent kinase inhibitor suppresses tumorigenicity in vivo.Nat Med,1995,1(10):1052-6
[14]Kumar A,Commane M,Flickinger TW,et al.Defective TNF-alpha-induced apoptosis in STATI-null cells due to low constitutive levels of caspases.Science,1997,278(5343):1630-2.
[15]Yu H,Jove R.The STATs of cancer--new molecular targets come of age.Nat Rev Cancer,2004,4(2):97-105.
[16]Stephanou A,Latchman DS.STAT-1:a novel regulator of apoptosis.Int J Exp Pathol,2003,84(6):239-44.
[17]Baldin V,Lukas J,Marcote MJ,Pagano M,Draetta G..Cyclin D1 is a nuclear protein required for cell cycle progression in G1.Genes Dev 1993,7(5):812-21.
[18]Bremnes RM,Veve R,Hirsch FR,et al.The E-cadherin cell-cell adhesion complex and lung cancer invasion,metastasis,and prognosis.Lung Cancer,2002,36(2):115-124.
[19]Bukholm IK,Nesland JM,Karesen R,et al.E-cadherin and alpha-,beta-,and gamma-catenin protein expression in relation to metastasis in human breast carcinoma.Pathol,1998,185(3):262-266.
[20]JW Chen,Konan Peck,Tse-Ming Hong,et al.Global Analysis of Gene Expression in Invasion by a Lung Cancer Model.Cancer research,2001,61(12):5223-5230.
[21]Edmondson HA,Steiner PE.Primery carcinoma of the liver:a study of 100 case among 48.900 necropsies.Cancer.1954,7(3):462-504.
[22]Tsal MF,Wang CC,Chang GC,et al.A New Tumor Suppressor DnaJ-like Heat Shock Protein,HLJ1,and Survival of Patients With Non - Small-Cell Lung Carcinoma[J].Journal of the National Cancer Institute,2006,98(12):825-838.
[23]Wang CC,Tsai MF.The transcriptional factor YY1 upregulates the novel invasion suppessor HLJ1 expression and inhibits cancer cell invasion.Oncogene,2005,24(25):4081-4093.
[24]Poon RT,Fan ST,et al.Different risk factors and prognosis for early and the late intrahepatic recurrence after resection of hepatocellular carcinama.Cancer, 2000,89(3):500-507.
[25] Shimada K,Sano T,Sakamoto Y,et al.A long-term follow-up and management study of hepatocellular carcinama patients surviving for 10 years or longer after curative hepatectomy.Cancer,2005,104(9):39-47
[26] Kaibori M, Matsui Y, Saito T, et al. Risk factors for different patterns of recurrence after resection of hepatocellular carcinoma. Anticancer Res. 2007; 27(4):2809-16.
[27] Shimada K, Sakamoto Y, Esaki M, et al. Analysis of prognostic factors affecting survival after initial recurrence and treatment efficacy for recurrence in patients undergoing potentially curative hepatectomy for hepatocellular carcinoma. Ann Surg Oncol. 2007;14(8):2337-47.
[28] Shimozawa N, Hanazaki K. Longterm prognosis after hepatic resection for small hepatocellular carcinoma. J Am Coll Surg. 2004;198(3):356-65.
[29] Yamada H, Kondo S, Okushiba S, et al. Analysis of predictive factors for recurrence after hepatectomy for colorectal liver metastases. World J Surg. 2001 ;25(9): 1129-33.
[30] Gruenberger T, Jourdan JL, Zhao J, et al. Echogenicity of liver metastases is an independent prognostic factor after potentially curative treatment. Arch Surg. 2000;135(11):1285-90.
[1]Lee GJ,Vierling E.A small heat shock protein cooperates with heat shock protein 70 systems to reactivate a heat-denatured protein.Plant Physiol,2000,122(1):189-198.
[2]Zatloukal K,Stumptner C,Fuchsbichler A,et al.p62 is a common component of cytoplasmic inclusions in protein aggregation diseases.Am J Pathol,2002,160(1):255-263.
[3]Park HS,Lee JS,Huh SH,et al.Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase.EMBO J,2001,20(3):446-456.
[4]Kasi VS,Kuppuswamy D.Inhibition of src family kinase by a combinatorial action of 5-AMP and small heat shock proteins identified from the adult heat.Mol Cell Biol,1999,19(10):6858-6871.
[5]Stangl K,Gunther C,Frank T,et al.Inhibition of the Ublquitln-Proteasome Pathway Induces Differential Heat-Shoek Protein Response in Cardiomyocytes and Renders Early Cardiac Protection.BiochemBiophys Res Commun,2002,291(3):542-549.
[6]Lu AL,Xu CS.Effects of heat shock on change of HSC70/HSP68 acid and alkaline phosphatases before and after rat partial hepatectomy.World J Gastroenterol,2000,6(5):730-733.
[7]Tsai MF,Wang CC,Chang GC,et al.A New Tumor Suppressor DnaJ-like Heat Shock Protein,HLJ1,and Survival of Patients With Non-Small Cell Lung Carcinoma.Journal of the National Cancer Institute,2006,98(12):825-838.
[8]Hoe KL,Won M,Chung KS,et al.Isolation of a new member of DnaJ-like heat shock protein 40(Hsp40)from human liver.Biochimica et Biophysica Acta, 1998,1383(1):4-8.
[9] Wang CC, Tsai MR The transcriptional factor YY1 upregulates the novel invasion suppessor HLJ1 expression and inhibits cancer cell invasion. Oncogene, 2005,24(25):4081-4093.
[10] Hattori H, Liu YC, Tohnai I, et al. Intracellular localization and partial amino acid sequence of a stress-inducible 40kDa protein in HeLa cells. Cell Struct. Funct. 1992,17(1 ):77 - 86.
[11] Ohtsuka K. Cloning of a cDNA for heat-shock protein hsp40 a human homologue of bacterial DnaJ. Res Commun. 1993,197(1):235 - 240.
[12] Qian YQ, Patel D, Hartl FU, et al. Nuclear magnetic resonance solution structure of the human Hsp40 (HDJ-1) J-domain. Mol Biol, 1996, 260(2): 224-35.
[13] Freeman BC, Myers MP, Schumacher R, et al. Identification of a regulatory motif in Hsp70 that affects ATPase activity, substrate binding and interaction with HDJ-1. EMBO J, 1995,14(10):2281-2292.
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