MTA1和SLP-2在宫颈鳞癌组织中的表达及临床意义
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摘要
背景与目的
宫颈癌是仅次于乳腺癌之后,最常见的妇科恶性肿瘤之一,每年新发现的病例大多数集中在发展中国家,特别是贫困地区,近年来其发病有年轻化的趋势,以宫颈鳞状细胞浸润癌为主,总体预后不佳,对我国女性的健康和生命安全造成了严重威胁。高危型人乳头瘤病毒(HPV)持续感染是宫颈癌的主要病因,但并不是唯一因素,宫颈癌的发生发展是多因素、多阶段、多步骤共同作用的结果,因此需要进一步寻找和研究有临床意义的和宫颈癌相关的指标。近年研究发现转移相关基因1(metastasis-associated gene1,MTA1)是一个与肿瘤转移相关的基因；目前关于SLP-2(stomatin-like protein2)蛋白在多种肿瘤组织中的研究显示：与正常配对的多种肿瘤组织中,SLP-2蛋白的表达是上调的,而SLP-2在宫颈癌组织中的研究较少,在宫颈癌组织中SLP-2的表达是上调还是下调?与临床病理参数之间的关系如何?是否与MTA1具有相关性?就是本文研究的重点。
材料与方法
1、标本来源：收集2011年5月至2012年5月在郑州大学第二附属医院妇产科因子宫肌瘤行子宫全切术的正常宫颈组织48例(A组)、宫颈上皮内瘤变(cervical intraepithelial neoplasia CIN)患者的宫颈组织43例(B组)、术前未经放化疗且有明确病理诊断的宫颈鳞癌组织42例(C组),并采集病理科存档的蜡块标本。
2、实验方法：采用免疫组化法检测不同宫颈组织中MTA1蛋白和SLP-2蛋白的表达及分布,RT-PCR法检测不同宫颈组织中MTA1mRNA和SLP-2mRNA的水平变化。
3、统计方法：采用SPSS17.0统计软件包进行数据分析,定量资料的比较采用t检验和单因素方差分析,率的比较采用χ2检验,相关性分析采用2×2配对资料的关联性分析和pearson相关分析。检验水准a=0.05(双侧)。
结果
1、MTA1的表达情况：在正常宫颈组织MTA1蛋白主要定位于细胞核,CIN及宫颈鳞癌MTA1蛋白出现了细胞膜、细胞核和细胞浆多种形式的蛋白定位,MTA1蛋白在A组、B组及C组中的阳性表达呈上升趋势,MTA1mRNA在A组、B组及C组中的表达水平亦呈上升趋势,在A组中的表达显著低于B组(P<0.05)及C组(P<0.05),而B组中MTA1的表达低于C组,但无统计学意义(P>0.05)。MTA1蛋白和MTAlmRNA在宫颈鳞癌中的过表达与患者的年龄、临床分期、组织分化程度、肿瘤大小无关(P>0.05),而与患者的淋巴结转移、肿瘤浸润深度密切相关(P<0.05)。宫颈鳞癌患者有淋巴结转移和随着肿瘤浸润深度的加深,MTA1蛋白的过表达有升高的趋势。
2、SLP-2的表达情况：在正常宫颈组织中SLP-2蛋白主要定位在细胞浆和细胞膜,CIN及宫颈鳞癌中SLP-2蛋白主要表现为细胞浆染色。SLP-2蛋白的阳性表达在A组、B组及C组中呈下降趋势,SLP-2mRNA的表达水平在A组、B组及C组中亦呈下降趋势,在C组中的表达明显低于A组(P<0.05)及B组(P<0.05),而B组中SLP-2的表达明显低于A组(P<0.05)。SLP-2的表达与宫颈鳞癌患者的年龄、临床分期、有无淋巴结转移、肿瘤浸润深度、肿瘤大小无相关性(P>0.05),而与组织分化程度相关,随着分化程度的增高,SLP-2的表达水平也有所增高(P=0.033)。
3、宫颈鳞癌组中MTA1和SLP-2表达的相关性：宫颈鳞癌组中MTA1蛋白和SLP-2蛋白的表达呈负相关(r=-0.393,P=0.037); MTA1mRNA和SLP-2mRNA的表达水平亦成负相关(r=-0.327,P=0.025)。
结论
1、MTA1在宫颈鳞癌组织中高表达,其表达与肿瘤的淋巴结转移、肿瘤浸润深度密切相关,提示MTA1与宫颈鳞癌的发生发展有关,可作为判断宫颈鳞癌恶性程度的指标。
2、SLP-2在宫颈鳞癌组织中低表达,与肿瘤分化程度相关,要明确SLP-2参与宫颈鳞癌发生发展的分子机制还有待进一步研究。
3、MTA1和SLP-2在宫颈鳞癌中的表达呈负相关,MTA1高表达和SLP-2低表达可能与宫颈鳞癌发生发展有关。
Background and Objective
Cervical carcinoma is the most common malignant tumors in female bodies, and the incidence rate of which is slightly higher than breast cancer. Every year83%of new cases are in developing countries, with the tendency that the age is getting younger. Of all the cases, cervical squamous cell carcinoma is the most common type, this situation being severe, thus threatening the health and life of the female in our country. The continuous infection of High-risk Human papilla virus (HPV) makes up the major cause of cervical carcinoma; however, it is not the only reason. The incidence and development of it is the result of various reasons, with several phases and steps, on this account, indicators concerning clinical significance should be consulted. Recently researches have found that metastasis-associated gene1(MTA1) is a sort of gene related to tumor metastasis; also, researches on the SLP-2(stomatin-like protein2) protein to various tumor have found that to various tumors of proper pairing, the expression of SLP-2in tumor tissue is Overexpressed, while there exists not much research of it in cervical carcinoma tissue. As a result, this paper focuses on the following issues:whether the expression in tumor tissue is upexpressed or downexpressed; the relationship between SLP-2and clinic-pathological parameters, and whether SLP-2is relative to MTA1.
Materials and methods:
1.Specimen origin:All samples are collected from the surgical excision tissue from May of2011to May of2012in the Second Affiliated Hospital of Zhengzhou University. The samples are divided as following:48cases of normal cervical tissue of total hysterectomy of uterine leiomyoma type(Group A);43cases of cervical intraepithelial neoplasia (CIN)(Group B);42cases of confirming pathological diagnosis of squamous carcinoma of the cervix without radiotherapy and chemotherapy before surgery(Group C). Samples of corresponding archival paraffin blocks in pathology department are also collected.
2.Experimental methods:immunohistochemistry techniques is adapted to detect the expression and distribution of MTA1and SLP-2in different cervical tissues. The method of RT-PCR to detect the changes in MTAlmRNA and SLP-2mRNA levels.
3.Statistical methods:SPSS17.0software package is adapted to analysis the data: both t test and one factor analysis of variance are adapted to examine the comparison of quantitative data,χ2to the comparison of rate, and2×2Correlation Analysis of paired data to relevance analysis. Inspection level:α=0.05(bilateral).
Results:
1.the expression of MTA1:in normal cervical tissues MTA1protein is mainly located in cell nucleuses while for CIN and MTA1in cervical carcinoma various protein location are found in the cell membranes, nucleuses and cytoplasm. The positive expression in Group A,B and C is overexpressed, and to same goes to the expression of MTAlmRNA. However the expression of latter in Group A is remarkably lower than Group B (P<0.05) and Group C (P<0.05). In Group B, the expression of MTA1is lower than Group C, but it has no statistical signification (P>0.05). the expression of MTA1in squamous carcinoma of the cervix has no relation to the age of the patient, clinical stages, degree of tissue differentiation, and the size of tumor (P>0.05), while it is highly related to lymphatic metastasis and the depth of myometrial invasion (P<0.05). the expression of MTA1will be upexpressed with the lymphatic metastasis of the patient and the deepening of the depth of myometrial invasion.
2.The expression of SLP-2:in normal cervical tissues SLP-2is mainly located in cell membranes and cytoplasm, while for CIN and SLP-2protein in cervical carcinoma is mainly expressed in the form of cytoplasm staining. The positive expression of SLP-2protein is downexpressed in Group A, B and C, and the same goes to the expression of SLP-2mRNA. The expression of the latter in Group C is obviously lower than that of Group A(P<0.05) and B (P<0.05). In Group B, the expression of SLP-2is obviously lower than Group A(P<0.05). The expression of SLP-2bears no relations with the age of the patient, clinical stages, the existence of lymphatic metastasis, the depth of myometrial invasion, and the size of tumor (P>0.05), while it is relative to the degree of tissue differentiation. With the increase of the degree of differentiation, the espression level of SLP-2is also increase (P=0.033).
3.The relativity of expression of MTA1and SLP-2in cervical carcinoma tissues: the expression of expression of MTA1and SLP-2in cervical carcinoma tissues is of inverse correlation(r=-0.393，P=0.037).
Conclusion:
1.The MTA1in cervical squamous cell carcinoma is of high expression, which is highly related to the lymphatic metastasis of tumors and the depth of myometrial invasion. The fact that MTA1is related to the occurrence and development of cervical carcinoma could be used as the index of the degree of malignancy of cervical squamous cell carcinoma.
2.The SLP-2in cervical squamous cell carcinoma is of low expression, which is probably a new cancer suppressor gene. It is relative to the degree of tissue differentiation, however, further research is required to confirm the molecular mechanism of SLP-2in the occurrence and development of cervical squamous cell carcinoma.
3.The expression of MTA1and SLP-2in cervical squamous cell carcinoma is of negative correlation, the high expression of MTAl and low expression of SLP-2is probably highly related to the occurrence and development of cervical squamous cell carcinoma as well as the biological behaviour.
宫颈癌是仅次于乳腺癌之后,最常见的妇科恶性肿瘤之一,每年新发现的病例大多数集中在发展中国家,特别是贫困地区,近年来其发病有年轻化的趋势,以宫颈鳞状细胞浸润癌为主,总体预后不佳,对我国女性的健康和生命安全造成了严重威胁。高危型人乳头瘤病毒(HPV)持续感染是宫颈癌的主要病因,但并不是唯一因素,宫颈癌的发生发展是多因素、多阶段、多步骤共同作用的结果,因此需要进一步寻找和研究有临床意义的和宫颈癌相关的指标。近年研究发现转移相关基因1(metastasis-associated gene1,MTA1)是一个与肿瘤转移相关的基因；目前关于SLP-2(stomatin-like protein2)蛋白在多种肿瘤组织中的研究显示：与正常配对的多种肿瘤组织中,SLP-2蛋白的表达是上调的,而SLP-2在宫颈癌组织中的研究较少,在宫颈癌组织中SLP-2的表达是上调还是下调?与临床病理参数之间的关系如何?是否与MTA1具有相关性?就是本文研究的重点。
材料与方法
1、标本来源：收集2011年5月至2012年5月在郑州大学第二附属医院妇产科因子宫肌瘤行子宫全切术的正常宫颈组织48例(A组)、宫颈上皮内瘤变(cervical intraepithelial neoplasia CIN)患者的宫颈组织43例(B组)、术前未经放化疗且有明确病理诊断的宫颈鳞癌组织42例(C组),并采集病理科存档的蜡块标本。
2、实验方法：采用免疫组化法检测不同宫颈组织中MTA1蛋白和SLP-2蛋白的表达及分布,RT-PCR法检测不同宫颈组织中MTA1mRNA和SLP-2mRNA的水平变化。
3、统计方法：采用SPSS17.0统计软件包进行数据分析,定量资料的比较采用t检验和单因素方差分析,率的比较采用χ2检验,相关性分析采用2×2配对资料的关联性分析和pearson相关分析。检验水准a=0.05(双侧)。
结果
1、MTA1的表达情况：在正常宫颈组织MTA1蛋白主要定位于细胞核,CIN及宫颈鳞癌MTA1蛋白出现了细胞膜、细胞核和细胞浆多种形式的蛋白定位,MTA1蛋白在A组、B组及C组中的阳性表达呈上升趋势,MTA1mRNA在A组、B组及C组中的表达水平亦呈上升趋势,在A组中的表达显著低于B组(P<0.05)及C组(P<0.05),而B组中MTA1的表达低于C组,但无统计学意义(P>0.05)。MTA1蛋白和MTAlmRNA在宫颈鳞癌中的过表达与患者的年龄、临床分期、组织分化程度、肿瘤大小无关(P>0.05),而与患者的淋巴结转移、肿瘤浸润深度密切相关(P<0.05)。宫颈鳞癌患者有淋巴结转移和随着肿瘤浸润深度的加深,MTA1蛋白的过表达有升高的趋势。
2、SLP-2的表达情况：在正常宫颈组织中SLP-2蛋白主要定位在细胞浆和细胞膜,CIN及宫颈鳞癌中SLP-2蛋白主要表现为细胞浆染色。SLP-2蛋白的阳性表达在A组、B组及C组中呈下降趋势,SLP-2mRNA的表达水平在A组、B组及C组中亦呈下降趋势,在C组中的表达明显低于A组(P<0.05)及B组(P<0.05),而B组中SLP-2的表达明显低于A组(P<0.05)。SLP-2的表达与宫颈鳞癌患者的年龄、临床分期、有无淋巴结转移、肿瘤浸润深度、肿瘤大小无相关性(P>0.05),而与组织分化程度相关,随着分化程度的增高,SLP-2的表达水平也有所增高(P=0.033)。
3、宫颈鳞癌组中MTA1和SLP-2表达的相关性：宫颈鳞癌组中MTA1蛋白和SLP-2蛋白的表达呈负相关(r=-0.393,P=0.037); MTA1mRNA和SLP-2mRNA的表达水平亦成负相关(r=-0.327,P=0.025)。
结论
1、MTA1在宫颈鳞癌组织中高表达,其表达与肿瘤的淋巴结转移、肿瘤浸润深度密切相关,提示MTA1与宫颈鳞癌的发生发展有关,可作为判断宫颈鳞癌恶性程度的指标。
2、SLP-2在宫颈鳞癌组织中低表达,与肿瘤分化程度相关,要明确SLP-2参与宫颈鳞癌发生发展的分子机制还有待进一步研究。
3、MTA1和SLP-2在宫颈鳞癌中的表达呈负相关,MTA1高表达和SLP-2低表达可能与宫颈鳞癌发生发展有关。
Background and Objective
Cervical carcinoma is the most common malignant tumors in female bodies, and the incidence rate of which is slightly higher than breast cancer. Every year83%of new cases are in developing countries, with the tendency that the age is getting younger. Of all the cases, cervical squamous cell carcinoma is the most common type, this situation being severe, thus threatening the health and life of the female in our country. The continuous infection of High-risk Human papilla virus (HPV) makes up the major cause of cervical carcinoma; however, it is not the only reason. The incidence and development of it is the result of various reasons, with several phases and steps, on this account, indicators concerning clinical significance should be consulted. Recently researches have found that metastasis-associated gene1(MTA1) is a sort of gene related to tumor metastasis; also, researches on the SLP-2(stomatin-like protein2) protein to various tumor have found that to various tumors of proper pairing, the expression of SLP-2in tumor tissue is Overexpressed, while there exists not much research of it in cervical carcinoma tissue. As a result, this paper focuses on the following issues:whether the expression in tumor tissue is upexpressed or downexpressed; the relationship between SLP-2and clinic-pathological parameters, and whether SLP-2is relative to MTA1.
Materials and methods:
1.Specimen origin:All samples are collected from the surgical excision tissue from May of2011to May of2012in the Second Affiliated Hospital of Zhengzhou University. The samples are divided as following:48cases of normal cervical tissue of total hysterectomy of uterine leiomyoma type(Group A);43cases of cervical intraepithelial neoplasia (CIN)(Group B);42cases of confirming pathological diagnosis of squamous carcinoma of the cervix without radiotherapy and chemotherapy before surgery(Group C). Samples of corresponding archival paraffin blocks in pathology department are also collected.
2.Experimental methods:immunohistochemistry techniques is adapted to detect the expression and distribution of MTA1and SLP-2in different cervical tissues. The method of RT-PCR to detect the changes in MTAlmRNA and SLP-2mRNA levels.
3.Statistical methods:SPSS17.0software package is adapted to analysis the data: both t test and one factor analysis of variance are adapted to examine the comparison of quantitative data,χ2to the comparison of rate, and2×2Correlation Analysis of paired data to relevance analysis. Inspection level:α=0.05(bilateral).
Results:
1.the expression of MTA1:in normal cervical tissues MTA1protein is mainly located in cell nucleuses while for CIN and MTA1in cervical carcinoma various protein location are found in the cell membranes, nucleuses and cytoplasm. The positive expression in Group A,B and C is overexpressed, and to same goes to the expression of MTAlmRNA. However the expression of latter in Group A is remarkably lower than Group B (P<0.05) and Group C (P<0.05). In Group B, the expression of MTA1is lower than Group C, but it has no statistical signification (P>0.05). the expression of MTA1in squamous carcinoma of the cervix has no relation to the age of the patient, clinical stages, degree of tissue differentiation, and the size of tumor (P>0.05), while it is highly related to lymphatic metastasis and the depth of myometrial invasion (P<0.05). the expression of MTA1will be upexpressed with the lymphatic metastasis of the patient and the deepening of the depth of myometrial invasion.
2.The expression of SLP-2:in normal cervical tissues SLP-2is mainly located in cell membranes and cytoplasm, while for CIN and SLP-2protein in cervical carcinoma is mainly expressed in the form of cytoplasm staining. The positive expression of SLP-2protein is downexpressed in Group A, B and C, and the same goes to the expression of SLP-2mRNA. The expression of the latter in Group C is obviously lower than that of Group A(P<0.05) and B (P<0.05). In Group B, the expression of SLP-2is obviously lower than Group A(P<0.05). The expression of SLP-2bears no relations with the age of the patient, clinical stages, the existence of lymphatic metastasis, the depth of myometrial invasion, and the size of tumor (P>0.05), while it is relative to the degree of tissue differentiation. With the increase of the degree of differentiation, the espression level of SLP-2is also increase (P=0.033).
3.The relativity of expression of MTA1and SLP-2in cervical carcinoma tissues: the expression of expression of MTA1and SLP-2in cervical carcinoma tissues is of inverse correlation(r=-0.393，P=0.037).
Conclusion:
1.The MTA1in cervical squamous cell carcinoma is of high expression, which is highly related to the lymphatic metastasis of tumors and the depth of myometrial invasion. The fact that MTA1is related to the occurrence and development of cervical carcinoma could be used as the index of the degree of malignancy of cervical squamous cell carcinoma.
2.The SLP-2in cervical squamous cell carcinoma is of low expression, which is probably a new cancer suppressor gene. It is relative to the degree of tissue differentiation, however, further research is required to confirm the molecular mechanism of SLP-2in the occurrence and development of cervical squamous cell carcinoma.
3.The expression of MTA1and SLP-2in cervical squamous cell carcinoma is of negative correlation, the high expression of MTAl and low expression of SLP-2is probably highly related to the occurrence and development of cervical squamous cell carcinoma as well as the biological behaviour.
引文
[1]Wang Y, Morrow JS. Identification and characterization of human SLP-2,a novel homologue of stomatin(band 7,2b)present in erythrocytes and other tissues[J]. J Biol Chem,2000, 275(11):8062-8071
[2]Da Cruz S, Parone PA, Gonzalo P, et al. SLP-2 interacts with prohibitins in the mitochondrial inner membrance and contributes to their stability[J]. Biochim Biophys Acta,2008,1783(5): 904-911
[3]Hampel H,Sweet,Westman JA,etal.Referral for cancer genetics consultation:a review and compilation of risk assessment criteria. J Med Genet,2004,41(2)81-91
[4]Manavathi B,Singh K,Kumar R,etal.MTA family of coreguletors in nuclear receptor biology and pathology[J]. Nucl Recept Signal,2007,30(5):0103
[5]Toh Y, Pencil SD,Nicolson GL. A novel candidatemetastasis-associated gene,mtal, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning,expression,and protein analyses[J]. J Biol chem,1994,269(37):22958-22963.
[6]黄永平,孟翔凌.MTA1与KISS-1在胃癌中的表达及临床病理意义[J].皖南医学院学报,2010,129(29)：259-262.
[7]张海利,王旭峰,温树信等.肿瘤相关基因1在喉鳞癌侵袭转移中的作用.中华实验外科学杂志[J],2011,28(2)：301-303.
[8]Dai YC, Zhu XS, Nan QZ, etal. Identification of differential gene expresions in colorectal cancer and polyp by cDNA microarray[J]. World J Gastroenterol.2012,18(6):570-5.
[9]饶玉梅,王鸿雁,范良生等.MTA1通过β-catenin、MMP-9调节HeLa细胞粘附、侵袭、转移.华中科技大学学报(医学版)[J],2011,40(1)：32-36.
[10]韩肖燕,钱海利,林晨等.宫颈癌中MTA1蛋白的表达及临床意义[J].实用妇产科杂志,2011,07(27)511-514.
[11]邓蕾,姜润秋,殷爱红等.肝细胞肝癌中MTAl基因的表达及其术后患者生存率及肿瘤复发率相关性研究[J]南京医科大学学报(自然科学版),2011,12(38)818-819.
[12]张海利,王旭峰,温树信等.肿瘤相关基因1在喉鳞癌侵袭转移中的作用.中华实验外科学杂志[J].2011,28(2)：301-303.
[13]韩肖燕,杨隽钧,向阳等,基因沉默MTA1对宫颈癌细胞生物学效应的影响[J].现代妇产科进展,2011,8(20)：594-596.
[14]刘海,胡俊波,王志强等.MTA1基因表达与人胃癌的浸润和转移[J].世界华人消化杂志,2006,14(34)3317.
[15]杨建伟.MTA1蛋白在肝癌组织中的表达及意义[J].重庆医学,2012,03,(41)：264-265.
[16]Hiebl-Dirschmied CM, Adolf GR, Prohaska R. Isolation and partial characte-rization of the human erythrocyte band 7 integral membrane protein.Biochim Biophys Acta.1991, 1065(2):195-202.
[17]Westberg JA, Entler B, Prohaska R, etal.The gene coding for erythrocyte protein band 7.2b(EPB72)is located in band q34.1 of human chromosome 9. Cytogenet Cell Genet.1993, 63(4):241-243.
[18]Hiebl-Dirschmied CM,Entle B,Glotzmann C,etal.Cloning and nucleotide sequence of cDNA encoding human erythrocyto band 7 Integral membrane protein.Biochim Biophys Acta.1991, 1090(1):123-124.
[19]Liu J, Deyoung SM, Zhang M, et al. The stomatin/prohibitin/flotillin/HFIK/C domain of flotillin-1 contains distinct sequeces that direct plasma membrance localization and protien interactions in 3T3-L1 adipocytes [J]. J Biol Chem,2005,280(16):16125-16134.
[20]冯旺琴,崔竹梅,冯凤芝,等.SLP-2 mRNA在子宫内膜癌中的表达及意义[J].中华妇产科杂志,2005,40(8)：553-557.
[21]曹文枫,张立勇,张斌等.SLP-2蛋白在食管鳞状细胞癌中的表达及其与肿瘤侵袭转移的关系[J].中华肿瘤杂志,2010,32(11)：830-833.
[22]张剑,李建生,吴敏等.SLP-2在胃癌中的表达及意义[J].世界华人消化杂志,2012,19(20)：1778-1781.
[23]Chang D, Ma K, Gong M, et al. SLP-2 overexression is associated with tumour distant metastasis and poor prognosis in pulmonary squarnous cell carcinoma[J]. Biomarkers,2010, 15(2):104-110.
[24]Cao W, Zhang B, Liu Y, et al. High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival[J]. Am J Clin Pathol, 2007,128(3):430-436.
[25]Cao WF, Zhang LY, Liu MB, et al. Prognostic significance of stomatin-like protein 2 overexpression in carngeal squamous cell carcinoma:clinical,histologic, and immunohistochemistry analysis with tissue microarray[J]. Hum Pathol,2007,38(5):747-752.
[26]吴郁.SLP-2基因在宫颈鳞癌组织中的表达及其功能的初步研究(D).北京：中国协和医科大学,2006.
[27]李莉.SLP-2在上皮性卵巢癌中的表达及其意义的探讨(D).青岛：青岛大学,2008.
[28]曹文枫,张立勇,张斌等.SLP-2基因在喉鳞状细胞癌和乳腺浸润性癌组织中的表达及其与预后的关系[J].中华病理学杂志,2010,32(5)：332-337.
[1]Jemal A, Murray T, Samuels A, etal. Cancer statitics. CA Cancer J Clin.2003,53:5-26.
[2]Bosch FX,Lorincz A,Munoz N,etal.The causal relation between human papillomrivus and cervical cancer J Clin Pathol.2002,55:244-265.
[3]Mori M,Sagae S.Recent programs in epidemiologic resarch of uterine cancer[J]. Can To Ka-ku Ryoho,2001,28(2):174-178.
[4]Ledwaba L,Dlamin Z,Naicker S,etal.Molecular genetics of human cervical cancerrole of papillomavirus and the apoptic cascade.Biol Chem.2004,385:671-682.
[5]Carrington M,Wang S,Martin MP,etal.Hierarchy of resistance to cervical neoplasis mediated by combinations of killer immuoglobulin-like receptor and human leukocyte antigen loci.J Exp Med.2005,201:1069-1075:
[6]Bekow AH, Gyllensten UB. Host genetic control of HPV 16 titer in carcinoma in situ of cervix uteri.Int J Cancer.2002,101:526-531.
[7]Bekow AH,Moberg M,Gyllensten UB.HLA class II allele control of HPV Load in carcinoma in situ of cervix uteri.Int J Cancer.2005,117:510-514.
[8]Cho NH,Lim SY,Kim YT,etal.G2 checkpoint in uterine cervical cancer with HPV16 E6 according to p53 polymorphism and its screening value.Gynecol oncol.2003,90:15-22.
[9]Toh Y,Pencil SD,Nicolson GL,etal.A novel candidate metastasis associted gene,mtal, differentially expressed in highly metasttic mammary adeno carcinoma cell lines.cDNA cloning,expression,and protein analysis[J]. Biol Chem,1994,269(37):22958-22966.
[10]Toh Y, Pencil SD, Nicolson GL, etal.Analysis of the conplete sequence of the novel metastasis-associated candidate gene,mtal,differentially expressed in mammary adenocarcinoma and breast cancer cell lines[J]. Gene,1995,159(1):97-104.
[11]Wang Y, Morrow JS. Identification and characterization of human SLP-2,a novel homologue of stomatin(band 7,2b)present in erythrocytes and other tissues[J]. J Biol Chem,2000, 275(11):8062-8071.
[12]Hiebl-Dirschmied CM, Adolf GR, Prohaska R. Isolation and partial characte-rization of the human erythrocyte band 7 integral membrane protein.Biochim Biophys Acta.1991, 1065(2):195-202.
[13]Westberg JA, Entler B, Prohaska R, etal.The gene coding for erythrocyte protein band 7.2b(EPB72)is located in band q34.1 of human chromosome 9.Cytogenet Cell Genet.1993, 63(4):241-243.
[14]Hiebl-Dirschmied CM, Entle B, Glotzmann C, etal. Cloning and nucleotide sequence of cDNA encoding human erythrocyto band 7 Integral membrane protein.Biochim Biophys Acta.1991,1090(1):123-124.
[15]Owczarek CM, Treutlein HR, Portbury KJ, Gulluyan LM, Kola I, Hertzog PJ. A novel member of the STOMATIN/EPB72/mec-2 family,stomatin-like 2(STOML2),is ubiquitously expressed and lacalizes to HAS chromosome 9p13.1.Cytogenet Cell Genet 2001, 92:196-203.
[16]Liu J, Deyoung SM, Zhang M, et al. The stomatin/prohibitin/flotillin/HFIK/C domain of flotillin-1 contains distinct sequeces that direct plasma membrance localization and protien interactions in 3T3-L1 adipocytes [J]. J Biol Chem,2005,280(16):16125-16134.
[17]Da Cruz S, Parone PA, Gonzalo P, et al. SLP-2 interacts with prohibitins in the mitochondrial inner membrance and contributes to their stability[J]. Biochim Biophys Acta,2008,1783(5): 904-911.
[18]Kumar R, Wang RA, Bagheri Y amand R, Emerging roles of MTA1 family members in human cancers[J]. Semin Oncol,2003,30(5):30.
[19]Mazumdar A, Wang RA, Mishra SK, etal Transcriptional repression of oestrogen receptor by metastasis associated protein 1 corepressor[J]. Nature Cell biology.2001,3(1):30-37.
[20]Yan C, Wang H, Toh Y, etal. Repression of 92-kDa type Ⅳ collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism,Which is both dependent on and independent of histone deacetylation[J]. J Bid Chem,2003,278(4):2309-2316.
[21]Moon HE, Cheon H, Lee MS, etal. Matastasis-associated 1 inhibits p53-induced apoptosis[J]. oncology reports,2007,18(5):1311-1314.
[22]Kheradmand F, Werner E, Tremble P, etal.Role of Racl and oxygen radicals in eollagenase-1 expression induced by cell shape change[J]. Science,1998,280(5365):898-902.
[23]Evers EE, Zondag GC, Malliri A, etal. Rho family proteins in celladhesion and cell migration[J]. Eur J Cancer,2000,36(10):1269-1274.
[24]Chevallet M, Lescuyer P, Diemer H, etal.Alterations of the mitochondrial proteome causes by the absense of mitochondrial DNA:a proteomic view [J].Electrophoresis,2006, 27(8):1574-1583.
[25]Pencil SD, Toh Y, Nicolson GL. Candidate metastasis-associated genes of the rat 13762NF mammary adenocarcinoma[J]. Breast Cancer Res Treat.1993,25(2):165-174.
[26]Iguchi H, Imura G, Toh Y, etal.Expression of MTA1, a metastasis-associated gene with histone deacetylase activity in pancreatic cancer[J]. Int J Oncol,2000,16(6):1211-1214.
[27]Sasakih, Morivama S, Nakashima Y, rtal. Expression of the MTA1Mrna in advanced lung cancer[J].Lung Cancer,2002,35(2):149-154.
[28]林川,陈汉,吴孟超,等.肿瘤转移基因MTA1的分子克隆及其在肝癌组织中表达的初步研究[J].中华普通外科杂志,2000,15(10)：634.
[29]饶玉梅,王鸿雁,范良生等.MTA1通过β-catenin、MMP-9调节HeLa细胞粘附、侵袭、转移.华中科技大学学报(医学版)[J],2011,40(1)：32-36.
[30]Soo Hyung Ryu, Young-Hwa Chung,Hyunseung Lee, etal. Metastatic Tumor Antigen 1 Is Closely Associated with Frequent Postperative Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma[J]. Hepatology,2008,47(3):929-936.
[31]Miyatani T, Kurita N, Mikami C, etal. Malignant potential of Barrets esophagus:special reference to HDAC-1 and MTA1 expression[J].Hepatogasteoenterology.2011,58(106):472-476.
[32]Ansgar Bruning, Josef Makovitzky, Andrea Gingelmaier, etal.The metastasis-associated genes MTA1 and MTA3 are abundantly expressed in human placenta and chorionic carcinoma cells Histochem Cell Biol 2009,132:33-38.
[33]Toh Y, Oki E, Oda S, etal. Overexpression of the MTA1 gene on gastrointestinal carcinomas: correlation with invasion and metastasis[J]. IntJ Cancer,1997,74(4):459-463.
[34]汪盛,彭程,蒋先镇,等.肿瘤转移基因MTA1在膀胱癌中的表达及其临床意义[J].中国医学工程.2007,15(17)：555-557.
[35]Rao Y, Wang H, Fan L, etal. Silencing MTA1 by RNAi reverses adhesion,migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53,and E-cadherin/β-catenin complex[J].Huazhong Univ Sci Technolog Med Sci,2011,31(1):1-9.
[36]Dannenmann C, Shabani N, Friese K, etal.The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer,represses Erbeta,and enhances expression of oncogenic cytokine GRO[J]. Cancer Biol Ther,2008,7(9):1460-1467.
[37]Park JO, Jung CK, Sun DI, etal. Relationships between metastasis-associsted protein(MTA)1 and lymphatic metastasis in tonsil cancer[J].Eur Arch Otorhinolaryngol.2011,268(9):1329-1334.
[38]GKawasaki S. Yanamoto I.Yoshitomi, etal.Overexpression of metastasis-associsted MTA1 in Oral squamous cell carcinomas：correlation with metastasis and invasion[J]. Oral Maxillofac. Surg.2008,37:1039-1046.
[39]Geng L, Deepak PA, Aija L, etal. identification of metastasis associsted antigen 1(MTA1) by serological screening of prostate cancer cDNA libraries[J].Open Biochem J.2008,2:100-107.
[40]Yang YM, Liu H, Li WB. etal.Expression of MTA1 and VEGF and their corelation in endometrial cancer[J].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi.2010,26(7):682-684.
[41]王会河,黄光武,莫立根,等.MTA1表达与鼻咽癌浸润转移的关系[J].广西医科大学学报,2006,23(4)：546-548.
[42]Adjei AA, Erlichman C, Sloan JA, etal. Phase I and pharmacologic study of sequences of gemcitabine and the multitargeted antifolate agent in patients with advanced solid tumors[J]. J Clin Oncol.2000,18(8):1748-1757.
[43]Stewart GW, Argent AC, Dash BC. stomatin:a putative cation transport regulator in the red cell membrane.Biochim Biophys Acta.1993,1225(1):15-25.
[44]Delaunay J,Stewart G, Iolascon A. Hereditary dehydrated and overhydrated stomatocytosis: recent advances.Curr Opin Hematol.1999,6(2):110-114.
[45]Innes DS, Sinard JH, Gilliga DM, etal. Exclusion of the stomatin,alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis. Am J Hematol.1999,60(1):72-74.
[46]Fricke B, Argent AC, Chetty MC, etal. The somatin gene and protein in overhydrated hereditary stomatocytosis. Blood.2003,102(6):2268-2277.
[47]张立勇,王涛,丁芳,等.SLP-2基因在食管鳞癌中的差异表达及其生物信息学分析。世界华人消化杂志,2004,12(7)：1517-1521.
[48]Stewart GW.The membrane defect in hereditarry stomatocytosis.Baillieres Clin Haematol.1993,6(2):371-399.
[49]苏雷,张建,魏秀琴,等.SLP-2基因的差异表达与肺癌的分化和转移.中国肿瘤临床,2005,32(12)：678-680.
[50]Guo QC, Shen JN, Jin S, etal. comparative proteomic analysis of human obteosarcoma and SV40-immortalized normal osteoblastic cell lines. Acta pharmacol Sin 2007,28(6): 850-858.
[51]Cao W, Zhang B, liu Y, etal. High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival.Am J Clin pathol 2007 128(3):430-436.
[52]Satoh K, Takeuchi M, Oda Y, etal.Identification of activity-regulated proteins in the postsynaptic density fraction. Genes Cells 2002,7(2):187-197.
[53]冯旺琴,崔竹梅,冯凤芝,等.SLP-2mRNA在子宫内膜癌中的表达及其意义.中华妇产科杂志,2005,40(8)：553-557.
[54]Cui Z, Zhang L, Hua Z, etal. stomatin-like protein 2 is overexpressed and related to cell growth in human endometrial adenocarcinoma Oncol Rep.2007,17(4):829-833.
[55]吴郁.SLP-2基因在宫颈鳞癌组织中的表达及其功能的初步研究(D).北京：中国协和医科大学,2006.
[56]Hainaut P, Hollstein M. Genetic steps in the development of squamous cell carcinoma of the esophagus[J]. Mutat Res,2000,462(2-3):335-342.
[57]Wagner E, Kircheis R, Walker G. Targeted nucleic acid delivery into tumors:new avenues fou cancer therapy.Biomedicine pharmacotherapy.2004,58:152-161.
[58]Hauwel M, Furon E, Gasque P. Molecular and cellular insights into the coxsackie-adenovirus receptor:role in cellular interactions in the stem cell niche.Brain Res Rev.2005,48:265-272.
[59]Deepa N, Nicola J, Willamson RJ, etal. Shedding of c-Met is regulatede by crosstalk by a TIMP-3 sensitive metalloproteinase. J Cell Sci.2000,114(5):1213-1220.
[60]You H, Liu Y, Prasad CK, etal. Multiple human papillomavirus genes affect the adeno-associated virus life cycle.Virology.2006,344(2):532-540.
[61]Baldus SE, Schwarz E, Lohrey C. Smad4 deficiency in cervical carcinoma cells. Oncogene. 2005,24(5):810-819.
[62]Jourdan M, Veyrune JL, Vos JD, etal. A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells. Oncogene.2003,22(19):2950-2959.
[63]Philipp B, Valentin D, Daniel MA, etal. Significant correlation of hypoxia-inducible factor-1 a with treatment outcome in cervical cncer treated with radical radiotherapy. Int J Radiation Oncology Biol Phys.2003,56:494-501.
[64]Wong CF, Bames LM, Dahler AL, etal. E2F modulates keratinocyte squamous differentiation: Implications fou E2F inhibition in squamous cell carcinoma. J Biol Chem.2003,278:28516- 28522.
[65]Santin AD, Zhan F, Bignotti E, etal. Gene expression profiles of primary HPV16 and HPV18 infected early stage cervical cancers and normal cervical epithelium:Identification of novel candidate molecular markers for cervical cncer diagnosis and therapy.Virology.2005, 331(2):269-291.
[66]Stommel JM, Wahl GM. A New Twist in the Feedback Loop:Stress-Activated MDM2 Destabilization is Required for p53 Activation.Cell Cycle.2005,4(3):411-417.
[67]Okino K, Konishi H, Doi D, etal.Up-regulation of growth factor receptor-bound protein 10 in cervical aquamous cell carcinoma.Oncol Rep,2005,13(6):1069-1074.
[68]Stack E, DuBois RN. Regulation of cyclo-oxygenase-2.Best Pract Res Clin Gastroenterol. 2001,15:787-800.
[69]Arias-Pulido H, Joste N, Wheeler CM, etal. Loss of heterozygosity on chromosome 6 in HPV-16 positive cervical carcinomas carrying the DRB1*1501-DQB1*0602 haplotype. Genes Chromosomes Cancer.2004,40:277-284.
[70]Kase H, Aoki Y, Tanaka.Fas ligand expression in cervical adenocarcino-marelevance to lymph node metastasis and tumor progression.Gynecol Oncol.2003,90:70-74.
[71]Jinan HQ, Quteba E, Nbrahem NM, etal. A novel function for tissue inhiitor of VEGF binding to VEGF receptor-2.Nature medicine.2003,9(4):407-415.
[72]Steenbergen BD, Kramer D, Braakhuis BJ, etal. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst.2004,96:294-305.
[73]Tebes SJ, Kruk PA. The genesis of RNA interference,its potential clinical applications, and implications in gynecologic cancer.Gynecol Oncol.2005,99(3):736-741.
[74]Nakata Y, Kim TK, Shetzline S, Gewirtz AM.Nucleic acid modulation of gene expression:approaches for nucleic acid therapeutics againt cancer.Crit Rev Eukaryot Gene Expr.2005,15(2):163-182.
[2]Da Cruz S, Parone PA, Gonzalo P, et al. SLP-2 interacts with prohibitins in the mitochondrial inner membrance and contributes to their stability[J]. Biochim Biophys Acta,2008,1783(5): 904-911
[3]Hampel H,Sweet,Westman JA,etal.Referral for cancer genetics consultation:a review and compilation of risk assessment criteria. J Med Genet,2004,41(2)81-91
[4]Manavathi B,Singh K,Kumar R,etal.MTA family of coreguletors in nuclear receptor biology and pathology[J]. Nucl Recept Signal,2007,30(5):0103
[5]Toh Y, Pencil SD,Nicolson GL. A novel candidatemetastasis-associated gene,mtal, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning,expression,and protein analyses[J]. J Biol chem,1994,269(37):22958-22963.
[6]黄永平,孟翔凌.MTA1与KISS-1在胃癌中的表达及临床病理意义[J].皖南医学院学报,2010,129(29)：259-262.
[7]张海利,王旭峰,温树信等.肿瘤相关基因1在喉鳞癌侵袭转移中的作用.中华实验外科学杂志[J],2011,28(2)：301-303.
[8]Dai YC, Zhu XS, Nan QZ, etal. Identification of differential gene expresions in colorectal cancer and polyp by cDNA microarray[J]. World J Gastroenterol.2012,18(6):570-5.
[9]饶玉梅,王鸿雁,范良生等.MTA1通过β-catenin、MMP-9调节HeLa细胞粘附、侵袭、转移.华中科技大学学报(医学版)[J],2011,40(1)：32-36.
[10]韩肖燕,钱海利,林晨等.宫颈癌中MTA1蛋白的表达及临床意义[J].实用妇产科杂志,2011,07(27)511-514.
[11]邓蕾,姜润秋,殷爱红等.肝细胞肝癌中MTAl基因的表达及其术后患者生存率及肿瘤复发率相关性研究[J]南京医科大学学报(自然科学版),2011,12(38)818-819.
[12]张海利,王旭峰,温树信等.肿瘤相关基因1在喉鳞癌侵袭转移中的作用.中华实验外科学杂志[J].2011,28(2)：301-303.
[13]韩肖燕,杨隽钧,向阳等,基因沉默MTA1对宫颈癌细胞生物学效应的影响[J].现代妇产科进展,2011,8(20)：594-596.
[14]刘海,胡俊波,王志强等.MTA1基因表达与人胃癌的浸润和转移[J].世界华人消化杂志,2006,14(34)3317.
[15]杨建伟.MTA1蛋白在肝癌组织中的表达及意义[J].重庆医学,2012,03,(41)：264-265.
[16]Hiebl-Dirschmied CM, Adolf GR, Prohaska R. Isolation and partial characte-rization of the human erythrocyte band 7 integral membrane protein.Biochim Biophys Acta.1991, 1065(2):195-202.
[17]Westberg JA, Entler B, Prohaska R, etal.The gene coding for erythrocyte protein band 7.2b(EPB72)is located in band q34.1 of human chromosome 9. Cytogenet Cell Genet.1993, 63(4):241-243.
[18]Hiebl-Dirschmied CM,Entle B,Glotzmann C,etal.Cloning and nucleotide sequence of cDNA encoding human erythrocyto band 7 Integral membrane protein.Biochim Biophys Acta.1991, 1090(1):123-124.
[19]Liu J, Deyoung SM, Zhang M, et al. The stomatin/prohibitin/flotillin/HFIK/C domain of flotillin-1 contains distinct sequeces that direct plasma membrance localization and protien interactions in 3T3-L1 adipocytes [J]. J Biol Chem,2005,280(16):16125-16134.
[20]冯旺琴,崔竹梅,冯凤芝,等.SLP-2 mRNA在子宫内膜癌中的表达及意义[J].中华妇产科杂志,2005,40(8)：553-557.
[21]曹文枫,张立勇,张斌等.SLP-2蛋白在食管鳞状细胞癌中的表达及其与肿瘤侵袭转移的关系[J].中华肿瘤杂志,2010,32(11)：830-833.
[22]张剑,李建生,吴敏等.SLP-2在胃癌中的表达及意义[J].世界华人消化杂志,2012,19(20)：1778-1781.
[23]Chang D, Ma K, Gong M, et al. SLP-2 overexression is associated with tumour distant metastasis and poor prognosis in pulmonary squarnous cell carcinoma[J]. Biomarkers,2010, 15(2):104-110.
[24]Cao W, Zhang B, Liu Y, et al. High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival[J]. Am J Clin Pathol, 2007,128(3):430-436.
[25]Cao WF, Zhang LY, Liu MB, et al. Prognostic significance of stomatin-like protein 2 overexpression in carngeal squamous cell carcinoma:clinical,histologic, and immunohistochemistry analysis with tissue microarray[J]. Hum Pathol,2007,38(5):747-752.
[26]吴郁.SLP-2基因在宫颈鳞癌组织中的表达及其功能的初步研究(D).北京：中国协和医科大学,2006.
[27]李莉.SLP-2在上皮性卵巢癌中的表达及其意义的探讨(D).青岛：青岛大学,2008.
[28]曹文枫,张立勇,张斌等.SLP-2基因在喉鳞状细胞癌和乳腺浸润性癌组织中的表达及其与预后的关系[J].中华病理学杂志,2010,32(5)：332-337.
[1]Jemal A, Murray T, Samuels A, etal. Cancer statitics. CA Cancer J Clin.2003,53:5-26.
[2]Bosch FX,Lorincz A,Munoz N,etal.The causal relation between human papillomrivus and cervical cancer J Clin Pathol.2002,55:244-265.
[3]Mori M,Sagae S.Recent programs in epidemiologic resarch of uterine cancer[J]. Can To Ka-ku Ryoho,2001,28(2):174-178.
[4]Ledwaba L,Dlamin Z,Naicker S,etal.Molecular genetics of human cervical cancerrole of papillomavirus and the apoptic cascade.Biol Chem.2004,385:671-682.
[5]Carrington M,Wang S,Martin MP,etal.Hierarchy of resistance to cervical neoplasis mediated by combinations of killer immuoglobulin-like receptor and human leukocyte antigen loci.J Exp Med.2005,201:1069-1075:
[6]Bekow AH, Gyllensten UB. Host genetic control of HPV 16 titer in carcinoma in situ of cervix uteri.Int J Cancer.2002,101:526-531.
[7]Bekow AH,Moberg M,Gyllensten UB.HLA class II allele control of HPV Load in carcinoma in situ of cervix uteri.Int J Cancer.2005,117:510-514.
[8]Cho NH,Lim SY,Kim YT,etal.G2 checkpoint in uterine cervical cancer with HPV16 E6 according to p53 polymorphism and its screening value.Gynecol oncol.2003,90:15-22.
[9]Toh Y,Pencil SD,Nicolson GL,etal.A novel candidate metastasis associted gene,mtal, differentially expressed in highly metasttic mammary adeno carcinoma cell lines.cDNA cloning,expression,and protein analysis[J]. Biol Chem,1994,269(37):22958-22966.
[10]Toh Y, Pencil SD, Nicolson GL, etal.Analysis of the conplete sequence of the novel metastasis-associated candidate gene,mtal,differentially expressed in mammary adenocarcinoma and breast cancer cell lines[J]. Gene,1995,159(1):97-104.
[11]Wang Y, Morrow JS. Identification and characterization of human SLP-2,a novel homologue of stomatin(band 7,2b)present in erythrocytes and other tissues[J]. J Biol Chem,2000, 275(11):8062-8071.
[12]Hiebl-Dirschmied CM, Adolf GR, Prohaska R. Isolation and partial characte-rization of the human erythrocyte band 7 integral membrane protein.Biochim Biophys Acta.1991, 1065(2):195-202.
[13]Westberg JA, Entler B, Prohaska R, etal.The gene coding for erythrocyte protein band 7.2b(EPB72)is located in band q34.1 of human chromosome 9.Cytogenet Cell Genet.1993, 63(4):241-243.
[14]Hiebl-Dirschmied CM, Entle B, Glotzmann C, etal. Cloning and nucleotide sequence of cDNA encoding human erythrocyto band 7 Integral membrane protein.Biochim Biophys Acta.1991,1090(1):123-124.
[15]Owczarek CM, Treutlein HR, Portbury KJ, Gulluyan LM, Kola I, Hertzog PJ. A novel member of the STOMATIN/EPB72/mec-2 family,stomatin-like 2(STOML2),is ubiquitously expressed and lacalizes to HAS chromosome 9p13.1.Cytogenet Cell Genet 2001, 92:196-203.
[16]Liu J, Deyoung SM, Zhang M, et al. The stomatin/prohibitin/flotillin/HFIK/C domain of flotillin-1 contains distinct sequeces that direct plasma membrance localization and protien interactions in 3T3-L1 adipocytes [J]. J Biol Chem,2005,280(16):16125-16134.
[17]Da Cruz S, Parone PA, Gonzalo P, et al. SLP-2 interacts with prohibitins in the mitochondrial inner membrance and contributes to their stability[J]. Biochim Biophys Acta,2008,1783(5): 904-911.
[18]Kumar R, Wang RA, Bagheri Y amand R, Emerging roles of MTA1 family members in human cancers[J]. Semin Oncol,2003,30(5):30.
[19]Mazumdar A, Wang RA, Mishra SK, etal Transcriptional repression of oestrogen receptor by metastasis associated protein 1 corepressor[J]. Nature Cell biology.2001,3(1):30-37.
[20]Yan C, Wang H, Toh Y, etal. Repression of 92-kDa type Ⅳ collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism,Which is both dependent on and independent of histone deacetylation[J]. J Bid Chem,2003,278(4):2309-2316.
[21]Moon HE, Cheon H, Lee MS, etal. Matastasis-associated 1 inhibits p53-induced apoptosis[J]. oncology reports,2007,18(5):1311-1314.
[22]Kheradmand F, Werner E, Tremble P, etal.Role of Racl and oxygen radicals in eollagenase-1 expression induced by cell shape change[J]. Science,1998,280(5365):898-902.
[23]Evers EE, Zondag GC, Malliri A, etal. Rho family proteins in celladhesion and cell migration[J]. Eur J Cancer,2000,36(10):1269-1274.
[24]Chevallet M, Lescuyer P, Diemer H, etal.Alterations of the mitochondrial proteome causes by the absense of mitochondrial DNA:a proteomic view [J].Electrophoresis,2006, 27(8):1574-1583.
[25]Pencil SD, Toh Y, Nicolson GL. Candidate metastasis-associated genes of the rat 13762NF mammary adenocarcinoma[J]. Breast Cancer Res Treat.1993,25(2):165-174.
[26]Iguchi H, Imura G, Toh Y, etal.Expression of MTA1, a metastasis-associated gene with histone deacetylase activity in pancreatic cancer[J]. Int J Oncol,2000,16(6):1211-1214.
[27]Sasakih, Morivama S, Nakashima Y, rtal. Expression of the MTA1Mrna in advanced lung cancer[J].Lung Cancer,2002,35(2):149-154.
[28]林川,陈汉,吴孟超,等.肿瘤转移基因MTA1的分子克隆及其在肝癌组织中表达的初步研究[J].中华普通外科杂志,2000,15(10)：634.
[29]饶玉梅,王鸿雁,范良生等.MTA1通过β-catenin、MMP-9调节HeLa细胞粘附、侵袭、转移.华中科技大学学报(医学版)[J],2011,40(1)：32-36.
[30]Soo Hyung Ryu, Young-Hwa Chung,Hyunseung Lee, etal. Metastatic Tumor Antigen 1 Is Closely Associated with Frequent Postperative Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma[J]. Hepatology,2008,47(3):929-936.
[31]Miyatani T, Kurita N, Mikami C, etal. Malignant potential of Barrets esophagus:special reference to HDAC-1 and MTA1 expression[J].Hepatogasteoenterology.2011,58(106):472-476.
[32]Ansgar Bruning, Josef Makovitzky, Andrea Gingelmaier, etal.The metastasis-associated genes MTA1 and MTA3 are abundantly expressed in human placenta and chorionic carcinoma cells Histochem Cell Biol 2009,132:33-38.
[33]Toh Y, Oki E, Oda S, etal. Overexpression of the MTA1 gene on gastrointestinal carcinomas: correlation with invasion and metastasis[J]. IntJ Cancer,1997,74(4):459-463.
[34]汪盛,彭程,蒋先镇,等.肿瘤转移基因MTA1在膀胱癌中的表达及其临床意义[J].中国医学工程.2007,15(17)：555-557.
[35]Rao Y, Wang H, Fan L, etal. Silencing MTA1 by RNAi reverses adhesion,migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53,and E-cadherin/β-catenin complex[J].Huazhong Univ Sci Technolog Med Sci,2011,31(1):1-9.
[36]Dannenmann C, Shabani N, Friese K, etal.The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer,represses Erbeta,and enhances expression of oncogenic cytokine GRO[J]. Cancer Biol Ther,2008,7(9):1460-1467.
[37]Park JO, Jung CK, Sun DI, etal. Relationships between metastasis-associsted protein(MTA)1 and lymphatic metastasis in tonsil cancer[J].Eur Arch Otorhinolaryngol.2011,268(9):1329-1334.
[38]GKawasaki S. Yanamoto I.Yoshitomi, etal.Overexpression of metastasis-associsted MTA1 in Oral squamous cell carcinomas：correlation with metastasis and invasion[J]. Oral Maxillofac. Surg.2008,37:1039-1046.
[39]Geng L, Deepak PA, Aija L, etal. identification of metastasis associsted antigen 1(MTA1) by serological screening of prostate cancer cDNA libraries[J].Open Biochem J.2008,2:100-107.
[40]Yang YM, Liu H, Li WB. etal.Expression of MTA1 and VEGF and their corelation in endometrial cancer[J].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi.2010,26(7):682-684.
[41]王会河,黄光武,莫立根,等.MTA1表达与鼻咽癌浸润转移的关系[J].广西医科大学学报,2006,23(4)：546-548.
[42]Adjei AA, Erlichman C, Sloan JA, etal. Phase I and pharmacologic study of sequences of gemcitabine and the multitargeted antifolate agent in patients with advanced solid tumors[J]. J Clin Oncol.2000,18(8):1748-1757.
[43]Stewart GW, Argent AC, Dash BC. stomatin:a putative cation transport regulator in the red cell membrane.Biochim Biophys Acta.1993,1225(1):15-25.
[44]Delaunay J,Stewart G, Iolascon A. Hereditary dehydrated and overhydrated stomatocytosis: recent advances.Curr Opin Hematol.1999,6(2):110-114.
[45]Innes DS, Sinard JH, Gilliga DM, etal. Exclusion of the stomatin,alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis. Am J Hematol.1999,60(1):72-74.
[46]Fricke B, Argent AC, Chetty MC, etal. The somatin gene and protein in overhydrated hereditary stomatocytosis. Blood.2003,102(6):2268-2277.
[47]张立勇,王涛,丁芳,等.SLP-2基因在食管鳞癌中的差异表达及其生物信息学分析。世界华人消化杂志,2004,12(7)：1517-1521.
[48]Stewart GW.The membrane defect in hereditarry stomatocytosis.Baillieres Clin Haematol.1993,6(2):371-399.
[49]苏雷,张建,魏秀琴,等.SLP-2基因的差异表达与肺癌的分化和转移.中国肿瘤临床,2005,32(12)：678-680.
[50]Guo QC, Shen JN, Jin S, etal. comparative proteomic analysis of human obteosarcoma and SV40-immortalized normal osteoblastic cell lines. Acta pharmacol Sin 2007,28(6): 850-858.
[51]Cao W, Zhang B, liu Y, etal. High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival.Am J Clin pathol 2007 128(3):430-436.
[52]Satoh K, Takeuchi M, Oda Y, etal.Identification of activity-regulated proteins in the postsynaptic density fraction. Genes Cells 2002,7(2):187-197.
[53]冯旺琴,崔竹梅,冯凤芝,等.SLP-2mRNA在子宫内膜癌中的表达及其意义.中华妇产科杂志,2005,40(8)：553-557.
[54]Cui Z, Zhang L, Hua Z, etal. stomatin-like protein 2 is overexpressed and related to cell growth in human endometrial adenocarcinoma Oncol Rep.2007,17(4):829-833.
[55]吴郁.SLP-2基因在宫颈鳞癌组织中的表达及其功能的初步研究(D).北京：中国协和医科大学,2006.
[56]Hainaut P, Hollstein M. Genetic steps in the development of squamous cell carcinoma of the esophagus[J]. Mutat Res,2000,462(2-3):335-342.
[57]Wagner E, Kircheis R, Walker G. Targeted nucleic acid delivery into tumors:new avenues fou cancer therapy.Biomedicine pharmacotherapy.2004,58:152-161.
[58]Hauwel M, Furon E, Gasque P. Molecular and cellular insights into the coxsackie-adenovirus receptor:role in cellular interactions in the stem cell niche.Brain Res Rev.2005,48:265-272.
[59]Deepa N, Nicola J, Willamson RJ, etal. Shedding of c-Met is regulatede by crosstalk by a TIMP-3 sensitive metalloproteinase. J Cell Sci.2000,114(5):1213-1220.
[60]You H, Liu Y, Prasad CK, etal. Multiple human papillomavirus genes affect the adeno-associated virus life cycle.Virology.2006,344(2):532-540.
[61]Baldus SE, Schwarz E, Lohrey C. Smad4 deficiency in cervical carcinoma cells. Oncogene. 2005,24(5):810-819.
[62]Jourdan M, Veyrune JL, Vos JD, etal. A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells. Oncogene.2003,22(19):2950-2959.
[63]Philipp B, Valentin D, Daniel MA, etal. Significant correlation of hypoxia-inducible factor-1 a with treatment outcome in cervical cncer treated with radical radiotherapy. Int J Radiation Oncology Biol Phys.2003,56:494-501.
[64]Wong CF, Bames LM, Dahler AL, etal. E2F modulates keratinocyte squamous differentiation: Implications fou E2F inhibition in squamous cell carcinoma. J Biol Chem.2003,278:28516- 28522.
[65]Santin AD, Zhan F, Bignotti E, etal. Gene expression profiles of primary HPV16 and HPV18 infected early stage cervical cancers and normal cervical epithelium:Identification of novel candidate molecular markers for cervical cncer diagnosis and therapy.Virology.2005, 331(2):269-291.
[66]Stommel JM, Wahl GM. A New Twist in the Feedback Loop:Stress-Activated MDM2 Destabilization is Required for p53 Activation.Cell Cycle.2005,4(3):411-417.
[67]Okino K, Konishi H, Doi D, etal.Up-regulation of growth factor receptor-bound protein 10 in cervical aquamous cell carcinoma.Oncol Rep,2005,13(6):1069-1074.
[68]Stack E, DuBois RN. Regulation of cyclo-oxygenase-2.Best Pract Res Clin Gastroenterol. 2001,15:787-800.
[69]Arias-Pulido H, Joste N, Wheeler CM, etal. Loss of heterozygosity on chromosome 6 in HPV-16 positive cervical carcinomas carrying the DRB1*1501-DQB1*0602 haplotype. Genes Chromosomes Cancer.2004,40:277-284.
[70]Kase H, Aoki Y, Tanaka.Fas ligand expression in cervical adenocarcino-marelevance to lymph node metastasis and tumor progression.Gynecol Oncol.2003,90:70-74.
[71]Jinan HQ, Quteba E, Nbrahem NM, etal. A novel function for tissue inhiitor of VEGF binding to VEGF receptor-2.Nature medicine.2003,9(4):407-415.
[72]Steenbergen BD, Kramer D, Braakhuis BJ, etal. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst.2004,96:294-305.
[73]Tebes SJ, Kruk PA. The genesis of RNA interference,its potential clinical applications, and implications in gynecologic cancer.Gynecol Oncol.2005,99(3):736-741.
[74]Nakata Y, Kim TK, Shetzline S, Gewirtz AM.Nucleic acid modulation of gene expression:approaches for nucleic acid therapeutics againt cancer.Crit Rev Eukaryot Gene Expr.2005,15(2):163-182.