T-cadherin分子在乳腺癌中的异常表达及意义
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摘要
目的:
通过检测乳腺癌组织、癌旁乳腺组织、乳腺纤维腺瘤、正常乳腺组织中T-cadherin的表达情况,分析不同乳腺组织中T-cadherin的表达差异;探讨T-cadherin的表达与乳腺癌临床病理因素的关系。
方法:
采用免疫组织化学SP法分别检测50例乳腺癌组织、20例癌旁乳腺组织、20例乳腺纤维腺瘤、10例正常乳腺组织中T-cadherin的表达情况,分析各组乳腺组织中T-cadherin的表达差异;分析T-cadherin的表达与乳腺癌临床病理因素的关系。
结果:
1、T-cadherin阳性染色主要位于细胞膜以及基底细胞的基底层,尤以细胞-细胞连接处最为明显,为浅黄色到棕黄色颗粒。本组中正常乳腺组织、纤维腺瘤乳腺组织、癌旁乳腺组织中绝大多数导管上皮细胞均呈强阳性或阳性染色,细胞浆内不染色;而在部分乳腺癌组织中肿瘤细胞黄色到棕黄色染色颗粒数目明显减少或不染色;部分肿瘤细胞胞浆内不同程度地发现T-cadherin异常表达分布(37例:浸润性导管癌31例,导管内癌3例,粘液腺癌2例,髓样癌1例)。T-cadherin在正常乳腺、纤维腺瘤乳腺组织、癌旁乳腺组织中的阳性表达率分别为100%(10/10)、95.0%(19/20)、95.0%(19/20);T-cadherin在乳腺癌组织中的阳性表达率仅为40%(20/50);经χ~2检验,T-cadherin在乳腺癌、癌旁乳腺组织、纤维腺瘤组织及正常乳腺组织中的阳性表达率差异有统计学意义(P＜0.001),进一步做两两比较(调整检验水准α′=0.0083),除乳腺癌组分别与癌旁乳腺组织、纤维腺瘤组织、正常乳腺组织三组之间有统计学差异外,其余三组分别做两两比较均无统计学差异。即T-cadherin在乳腺癌组织中的阳性表达率(40.0%)显著低于癌旁乳腺组织的95.0%(χ~2=8.333,P=0.004),低于纤维腺瘤组织的95:0%(χ~2=8.333,P=0.004),低于正常乳腺组织的100.0%(χ~2=11.20,P=0.001);而在癌旁乳腺组织、纤维腺瘤组织及正常乳腺组织间两两比较T-cadherin表达率无统计学差异(P＞0.0083)。
2、T-cadherin在乳腺癌组织中的表达率与TNM分期和腋窝淋巴结转移两因素相关,其中:TNM分期三组之间T-cadherin的表达率不全相同,Ⅲ、Ⅳ期的乳腺癌组织T-cadherin的阳性表达率仅为12.5%,明显低于Ⅰ期(60.0%)和Ⅱ期(47.4%)两组,三组之间差异有统计学意义(χ~2=7.971,P=0.019),进一步两两比较(调整检验水准α′=0.017),TNM分期Ⅰ期和TNM分期Ⅲ、Ⅳ期之间的的T-cadherin阳性表达率存在显著统计学差异(确切概率法计算得P=0.009),TNM分期Ⅲ、Ⅳ期的T-cadherin阳性表达率显著低于TNM分期Ⅰ期的阳性表达率;而TNM分期Ⅰ期和TNM分期Ⅱ期、TNM分期Ⅱ期和TNM分期Ⅲ、Ⅳ期之间T-cadherin的表达率无统计学差异(确切概率法计算分别得P=0.51;P=0.035)。有腋窝淋巴结转移的患者T-cadherin阳性表达率低于无腋窝淋巴结转移患者的阳性表达率(χ~2=5.556,P=0.018)。T-cadherin在乳腺癌组织中的表达率与患者年龄、肿瘤瘤体直径大小,组织学分级、ER、PR、Cer-bB-2等因素无显著相关,差异无统计学意义。
结论:
1、乳腺癌组织中的T-cadherin分子的阳性表达率较癌旁乳腺组织、乳腺纤维腺瘤组织和正常乳腺组织显著下调(减少或缺失),差异有统计学意义,我们推测其在肿瘤发生、发展的过程中可能扮演抑癌基因的角色。
2、乳腺癌组织中T-cadherin分子表达下调与肿瘤TNM分期以及腋窝淋巴结转移等因素密切相关,提示随着肿瘤的恶性进展,T-cadherin分子的表达进行性下降。
Objective:By detecting breast cancer,adjacent normal tissues,breast fibroadenoma and normal breast tissue in T-cadherin expression,analysis of different breast tissues between T-cadherin expression;of T-cadherin Expression in Breast factors.
Methods:Immunohistochemical SP method were detected in 50 cases of breast cancer,20 cases of adjacent normal tissues,20 cases of breast fibroadenoma,10 cases of normal breast tissue T-cadherin expression,analysis of breast tissue in each group T-cadherin Differential expression;of T-cadherin expression and clinical pathological factors in breast cancer.
Results:
1、T-cadherin staining was mainly located in the basal membrane and basal cells, especially cells-cells displayed the most obvious,is light yellow to brown granules. The group of normal breast tissue,fibroadenoma breast tissue,breast tissue most adjacent ductal epithelial cells were strongly positive or positive staining, non-staining cytoplasm;in some tumor cells in breast cancer yellow to brown The number of yellow stained particles significantly reduced or non-staining,and the cytoplasm of tumor cells were found to varying degrees,abnormal expression of T-cadherin distribution(37 cases:31 cases of invasive ductal carcinoma,ductal carcinoma in 3 patients,2 cases of mucinous adenocarcinoma,Medullary carcinoma 1 case),
T-cadherin in normal breast,fibroadenoma of breast tissue,adjacent normal tissues,the positive expression rate was 100%(10/10),95.0%(19/20),95.0%(19/20); T- cadherin in breast cancer,the positive expression rate was 40%(20/50);by the test χ~2,T-cadherin in breast cancer,adjacent normal tissues,tumor tissues and normal breast tissue expression of positive difference statistically significant(P＜0.001),and further to do 22 more(adjusted test leveα'=0.0083),respectively,than breast cancer group and in adjacent normal tissues,tumor tissues,normal breast tissue were significantly different between the three groups of foreign The other three groups were doing 22 There were no significant differences.That T-cadherin in breast cancer positive expression rate(40.0%) was significantly lower than in adjacent normal tissues of 95.0%(χ~2=8.333,P=0.004),lower than the tumor tissues of 95.0%(χ~2= 8.333,P=0.004),lower than normal breast tissue of 100.0%(χ~2=11.20,P=0.001); and in adjacent normal tissues,tumor tissues and normal breast tissue and comparisons between T-cadherin expression was not significant(P＞0.0083). 2、T-cadherin expression in breast cancer rates with TNM stage and lymph node metastasis associated with two factors,including:TNM stages between the three groups T-cadherin expression in the same failure rate,Ⅲ、Ⅳstage breast cancer T-cadherin positive expression rate was 12.5%,significantly lower than in stageⅠ(60.0%) andⅡ(47.4%) groups,the differences between the three groups was statistically significant(χ~2=7.971,P=0.019),further 22 more(adjusted test leveα'= 0.017),TNM stage and TNM stageⅠ,Ⅲ、Ⅳperiod between the T-cadherin expression and there was significant statistical difference(calculated exact test P= 0.009),TNM stageⅢ、Ⅳstage of T-cadherin expression was significantly lower than the TNM stageⅠ,the positive rate;and TNM staging TNM stageⅠandⅡstage, TNM stage and TNM stageⅡ,Ⅲ、Ⅳof expression between T-cadherin was no significant difference(exact probability method was,respectively P=0.51;P=0.035). Patients with axillary lymph node T-cadherin expression was lower than in patients without axillary lymph node positive rate(χ~2=5.556,P=0.018).T-cadherin expression in breast cancer rates with age,tumor diameter,tumor size,histological grade,ER,PR,Cer-bB-2 and other factors not significant,the difference was not statistically significant.
Conclusions.
1、Breast Cancer T-cadherin molecule expression rate than in noncancerous breast tissue,breast tumor tissues and normal breast tissue was significantly reduced (decrease or absence),in cancer development and the process may play a tumor suppressor gene role.
2、Breast Cancer T-cadherin molecules down with tumor TNM stage and lymph node metastasis is closely related,suggesting that tumors with malignant progression, T-cadherin molecules were decreased.
通过检测乳腺癌组织、癌旁乳腺组织、乳腺纤维腺瘤、正常乳腺组织中T-cadherin的表达情况,分析不同乳腺组织中T-cadherin的表达差异;探讨T-cadherin的表达与乳腺癌临床病理因素的关系。
方法:
采用免疫组织化学SP法分别检测50例乳腺癌组织、20例癌旁乳腺组织、20例乳腺纤维腺瘤、10例正常乳腺组织中T-cadherin的表达情况,分析各组乳腺组织中T-cadherin的表达差异;分析T-cadherin的表达与乳腺癌临床病理因素的关系。
结果:
1、T-cadherin阳性染色主要位于细胞膜以及基底细胞的基底层,尤以细胞-细胞连接处最为明显,为浅黄色到棕黄色颗粒。本组中正常乳腺组织、纤维腺瘤乳腺组织、癌旁乳腺组织中绝大多数导管上皮细胞均呈强阳性或阳性染色,细胞浆内不染色;而在部分乳腺癌组织中肿瘤细胞黄色到棕黄色染色颗粒数目明显减少或不染色;部分肿瘤细胞胞浆内不同程度地发现T-cadherin异常表达分布(37例:浸润性导管癌31例,导管内癌3例,粘液腺癌2例,髓样癌1例)。T-cadherin在正常乳腺、纤维腺瘤乳腺组织、癌旁乳腺组织中的阳性表达率分别为100%(10/10)、95.0%(19/20)、95.0%(19/20);T-cadherin在乳腺癌组织中的阳性表达率仅为40%(20/50);经χ~2检验,T-cadherin在乳腺癌、癌旁乳腺组织、纤维腺瘤组织及正常乳腺组织中的阳性表达率差异有统计学意义(P＜0.001),进一步做两两比较(调整检验水准α′=0.0083),除乳腺癌组分别与癌旁乳腺组织、纤维腺瘤组织、正常乳腺组织三组之间有统计学差异外,其余三组分别做两两比较均无统计学差异。即T-cadherin在乳腺癌组织中的阳性表达率(40.0%)显著低于癌旁乳腺组织的95.0%(χ~2=8.333,P=0.004),低于纤维腺瘤组织的95:0%(χ~2=8.333,P=0.004),低于正常乳腺组织的100.0%(χ~2=11.20,P=0.001);而在癌旁乳腺组织、纤维腺瘤组织及正常乳腺组织间两两比较T-cadherin表达率无统计学差异(P＞0.0083)。
2、T-cadherin在乳腺癌组织中的表达率与TNM分期和腋窝淋巴结转移两因素相关,其中:TNM分期三组之间T-cadherin的表达率不全相同,Ⅲ、Ⅳ期的乳腺癌组织T-cadherin的阳性表达率仅为12.5%,明显低于Ⅰ期(60.0%)和Ⅱ期(47.4%)两组,三组之间差异有统计学意义(χ~2=7.971,P=0.019),进一步两两比较(调整检验水准α′=0.017),TNM分期Ⅰ期和TNM分期Ⅲ、Ⅳ期之间的的T-cadherin阳性表达率存在显著统计学差异(确切概率法计算得P=0.009),TNM分期Ⅲ、Ⅳ期的T-cadherin阳性表达率显著低于TNM分期Ⅰ期的阳性表达率;而TNM分期Ⅰ期和TNM分期Ⅱ期、TNM分期Ⅱ期和TNM分期Ⅲ、Ⅳ期之间T-cadherin的表达率无统计学差异(确切概率法计算分别得P=0.51;P=0.035)。有腋窝淋巴结转移的患者T-cadherin阳性表达率低于无腋窝淋巴结转移患者的阳性表达率(χ~2=5.556,P=0.018)。T-cadherin在乳腺癌组织中的表达率与患者年龄、肿瘤瘤体直径大小,组织学分级、ER、PR、Cer-bB-2等因素无显著相关,差异无统计学意义。
结论:
1、乳腺癌组织中的T-cadherin分子的阳性表达率较癌旁乳腺组织、乳腺纤维腺瘤组织和正常乳腺组织显著下调(减少或缺失),差异有统计学意义,我们推测其在肿瘤发生、发展的过程中可能扮演抑癌基因的角色。
2、乳腺癌组织中T-cadherin分子表达下调与肿瘤TNM分期以及腋窝淋巴结转移等因素密切相关,提示随着肿瘤的恶性进展,T-cadherin分子的表达进行性下降。
Objective:By detecting breast cancer,adjacent normal tissues,breast fibroadenoma and normal breast tissue in T-cadherin expression,analysis of different breast tissues between T-cadherin expression;of T-cadherin Expression in Breast factors.
Methods:Immunohistochemical SP method were detected in 50 cases of breast cancer,20 cases of adjacent normal tissues,20 cases of breast fibroadenoma,10 cases of normal breast tissue T-cadherin expression,analysis of breast tissue in each group T-cadherin Differential expression;of T-cadherin expression and clinical pathological factors in breast cancer.
Results:
1、T-cadherin staining was mainly located in the basal membrane and basal cells, especially cells-cells displayed the most obvious,is light yellow to brown granules. The group of normal breast tissue,fibroadenoma breast tissue,breast tissue most adjacent ductal epithelial cells were strongly positive or positive staining, non-staining cytoplasm;in some tumor cells in breast cancer yellow to brown The number of yellow stained particles significantly reduced or non-staining,and the cytoplasm of tumor cells were found to varying degrees,abnormal expression of T-cadherin distribution(37 cases:31 cases of invasive ductal carcinoma,ductal carcinoma in 3 patients,2 cases of mucinous adenocarcinoma,Medullary carcinoma 1 case),
T-cadherin in normal breast,fibroadenoma of breast tissue,adjacent normal tissues,the positive expression rate was 100%(10/10),95.0%(19/20),95.0%(19/20); T- cadherin in breast cancer,the positive expression rate was 40%(20/50);by the test χ~2,T-cadherin in breast cancer,adjacent normal tissues,tumor tissues and normal breast tissue expression of positive difference statistically significant(P＜0.001),and further to do 22 more(adjusted test leveα'=0.0083),respectively,than breast cancer group and in adjacent normal tissues,tumor tissues,normal breast tissue were significantly different between the three groups of foreign The other three groups were doing 22 There were no significant differences.That T-cadherin in breast cancer positive expression rate(40.0%) was significantly lower than in adjacent normal tissues of 95.0%(χ~2=8.333,P=0.004),lower than the tumor tissues of 95.0%(χ~2= 8.333,P=0.004),lower than normal breast tissue of 100.0%(χ~2=11.20,P=0.001); and in adjacent normal tissues,tumor tissues and normal breast tissue and comparisons between T-cadherin expression was not significant(P＞0.0083). 2、T-cadherin expression in breast cancer rates with TNM stage and lymph node metastasis associated with two factors,including:TNM stages between the three groups T-cadherin expression in the same failure rate,Ⅲ、Ⅳstage breast cancer T-cadherin positive expression rate was 12.5%,significantly lower than in stageⅠ(60.0%) andⅡ(47.4%) groups,the differences between the three groups was statistically significant(χ~2=7.971,P=0.019),further 22 more(adjusted test leveα'= 0.017),TNM stage and TNM stageⅠ,Ⅲ、Ⅳperiod between the T-cadherin expression and there was significant statistical difference(calculated exact test P= 0.009),TNM stageⅢ、Ⅳstage of T-cadherin expression was significantly lower than the TNM stageⅠ,the positive rate;and TNM staging TNM stageⅠandⅡstage, TNM stage and TNM stageⅡ,Ⅲ、Ⅳof expression between T-cadherin was no significant difference(exact probability method was,respectively P=0.51;P=0.035). Patients with axillary lymph node T-cadherin expression was lower than in patients without axillary lymph node positive rate(χ~2=5.556,P=0.018).T-cadherin expression in breast cancer rates with age,tumor diameter,tumor size,histological grade,ER,PR,Cer-bB-2 and other factors not significant,the difference was not statistically significant.
Conclusions.
1、Breast Cancer T-cadherin molecule expression rate than in noncancerous breast tissue,breast tumor tissues and normal breast tissue was significantly reduced (decrease or absence),in cancer development and the process may play a tumor suppressor gene role.
2、Breast Cancer T-cadherin molecules down with tumor TNM stage and lymph node metastasis is closely related,suggesting that tumors with malignant progression, T-cadherin molecules were decreased.
引文
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[36]Riou P,Saffroy R,ComoyJ,et al.Investigation in liver tissues and cell lines of the transcription of 13 genes mapping to the 16q24 region that are frequently deleted in hepatocellular carcinoma[J].Clin Cancer Res,2002,8:3178-3186.
[37]Yu J,Ni M,Xu J,et al.Methytation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocelludar carcinog-enesis[J].BMC Cancer,2002,2:29.
[38]黄志勇,陈孝平,吴在德,等.黏附分子T-cadherin抑制C6胶质母细胞瘤增殖与p21表达相关[J].中华实验外科杂志,2007,22(11):1304-1305.
[39]Philippova M,Joshi MB,Kyriakakis E,et al.A guide and guard:the many faces of T-cadherin[J].Cell Signal,2009,21(7):1035-1044.
[40]Takeuchi T,Liang SB,Ohtsuki Y.Downregulation of expression of a novel cadherin molecule,T-cadherin,in basal cell carcinomaof the skin[J].Mol Carcinog,2002,35(4):173-179.
[41]Roman-Gomez J,Castillejo JA,Jimenez A,et al.Cadherin-13,a mediator of calcium -dependent cell-cell adhesion,is silenced by methtylation in chronic myetoid leukemia and correlates with pretreatment risk profile and cytogenetic response to interferon atfa[J].J Clin Oncol,2003,21(8):1472-1479.
[42]Hibi K,Koshikawa K,Inoue S,et al.Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer[J].Cancer Sci.2004,95(7):588-591.
[43]Sakai M,Ogama Y,Ouchida M,et al.Prevalent hyper-methylation of the CDH13gene promoter in malignant B cell lymphomas[J].Int J Oncol,2004,25(3):685-691.
[44]Widschwendter A,Ivarsson L,BlassnigA,et al.CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients[J].Int J Cancer,2004,109(2):163-1661
[45]于波,程滨珠,钟绮丽,等.皮肤基底细胞癌T钙黏蛋白的表达及其DNA异常甲基化分析[J].中华皮肤科杂志,2007,40(3):152-154.
[46]Lee SW.H-cadherin,a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer[J].Nature Med,1996,2(?):776-782.
[47]Miki Y,Katagiri T,Nakamura Y.Infrequent mutation of the H-cadherin gene on chromosome 16q24 in human breast cancers[J].Jpn J Cancer Res,1997,88(8):701-704.
[48]Takeuchi T,Misaki A,Chert BK,et al.H-cadherin expression in breast cancer[J].Histopathology.1999,35(1):87-88.
[49]Toyooka KO,Toyooka S,Virmani AK,et al.Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas[J]. Cancer Res, 2001,61 (11): 4556-4560.
[50] Ivanov D, Philippova M, Allenspach R, et al, T-cadherin upregulation correlates with cell-cycle progression and promotes proliferation of vascular cells[J]. Gardiovasc Res,2004,64(1)132-143.
[51] Widschwendter A, Ivarsson L, Blassnig A, et al. CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients[J]. Int J Cancer, 2004,109(2):163-166.
[52] Lewis CM, Cler LR, Bu DW, et al. Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk[J]. Clin Cancer Res, 2005, 11(1): 410-411.
[1]Huang ZY,Wu Y,Hedrick N,et al.T-cadherin-mediated cell growth regulation involves G2 phase arrest and requires p21(CIP1/WAF1) expression[J].Mol Cell BioI,2003,23(2):566-578.PMID:1250945S[PubMed-indexed for MEDLINE].
[2]Kemler R.Classical cadherins[J].Semin Cell Biol,1992,3(3):149-155.PMID:1623204[PubMed-indexed for MEDLINE].
[3] Koller E, Ransch B. Differential targeting of T- and N-cadherin in polarized epithelial cells[J]. J Biol Chem, 1996, 271 (47) :30061-30067. PMID: 8939953 [PubMed - indexed for MEDLINE].
[4] Vestal DJ, Ranscht B. Glycosyl phosphatidylinositol-anchored T-cadherin mediates calcium-dependent, homophilic cell adhesion[J].J Cell Biol, 1992,119(2):451-461. PMID: 1400585 [PubMed - indexed for MEDLINE].
[5] Kipmen-Korgun D, Osibow K, Zoratti C, et al. T-cadherin mediates low-density lipoprotein-initiated cell proliferation via the Ca(2+)-tyrosine kinase-Erk1/2 pathway[J]. J Cardiovasc Pharmacol, 2005, 45(5):418-430. PMID: 15821437 [PubMed -indexed for MEDLINE].
[6] Simonneau L, Gallego M, Pujol R. Comparative expression patterns of T-, N-, E-cadherins, beta-catenin, and polysialic acid neural cell adhesion molecule in rat cochlea during development: implications for the nature of Kolliker's organ [J]. J Comp Neurol, 2003,459(2):113-126. PMID: 12640664 [PubMed - indexed for MEDLINE].
[7] Takeuchi T, Liang SB, Matsuyoshi N, et al. Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma[J]. Lab Invest, 2002, 82(8):1023-1029. PMID: 12177241 [PubMed - indexed for MEDLINE].
[8] Munro SB, Duclos AJ, Jackson AR, et al. Characterization of cadherins expressed by murine thymocytes[J]. Cell Immunol, 1996,169(2):309-312. PMID: 8620560 [PubMed - indexed for MEDLINE].
[9] Zhou S, Matsuyoshi N, Liang SB, et al, Expression of T-cadherin in Basal keratinocytes of skin[J]. J Invest Dermatol, 2002 ,118(6): 1080-1184. PMID: 12060406 [PubMed -indexed for MEDLINE].
[10] Philippova M, Ivanov D, Tkachuk V, et al, Polarisation of T-cadherin to the leading edge of migrating vascular cells in vitro: a function in vascular cell motility? [J]. Histochem Cell Biol,2003,120(5):353-360. PMID: 14579115 [PubMed-indexed for MEDLINE].
[11] Hug C, Wang J, Ahmad NS, et al, T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin[J]. Proc Natl Acad Sci U S A,2004, 101 (28):10308-10313. PMID: 15210937 [PubMed - indexed for MEDLINE].
[12]Sato M,Mori Y,Sakurada A,et al,The H-cadherin(CDH13) gene is inactivated in human lung cancer[]].Hum Genet,1998,103(1):96-101.PMID:9737784[PubMed -indexed for MEDLINE].
[13]Toyooka S,Toyooka KO,Harada K,et al,Aberrant methylation of the CDH13(H-cadherin) promoter region in colorectal cancers and adenomas[J].Cancer Res,2002,62(12):3382-3386.PMID:12067979[PubMed - indexed for MEDLINE].
[14]戴志慧,严群,李兆明,等.结直肠癌中T-cadherin分子表达异常及意义[J].华中科技大学学报·医学版,2008,37(1):121-122.
[15]Sun D,Zhang Z,Van do N,et al.Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker[J].Oral 0ncoi,2007,43(1):82-87.PMID:16807071[PubMed - indexed for MEDLINE].
[16]Hibi K,Nakao A.Lymph node metastasis is infrequent in patients with highly-methylated colorectal cancer[J].Anticancer Res,2006,26(1A):55-58 PMID:16475679[PubMed - indexed for MEDLINE].
[17]Jones PA,Takai D.The role of DNA methylation in mammalian epigenetics[J].Science,2001,293(5532):1068-1070.PMID:11498573[PubMed - indexed for MEDLINE].
[18]Takeuchi T,Misaki A,Liang SB,et al.Expression of T-cadherin(CDH13,H-Cadherin) in human brain and its characteristics as a negative growth regulator of epidermal growth factor in neuroblastoma cells[J].J Neurochem,2000,74(4):1489-1497.PMID:10737605[PubMed - indexed for MEDLINE].
[19]Lee SW,Reimer CL,Campbell DB,et al.H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo[J].Carcinogenesis,1998,19(6):1157-1159.PMID:9667758[PubMed - indexed for MEDLINE].
[20]梁治坤,黄志勇,陈孝平,等。5-杂氮-2′-脱氧胞苷诱导裸鼠HepG2种植瘤细胞T-cadherin的表达及其对种植瘤的抑制作用[J].世界华人消化杂志,2008,16(16):1741-1745.
[21]Ivanov D,Philippova M,Allenspach R,et al.T-cadherin upregulation correlates with cell-cycle progression and promotes proliferation of vascular cells[J].Cardiovasc Res,2004,64(I):132-43.PMID:15364621[PubMed - indexed for MEDLINE].
[2]Wheelock MJ,Soler AP,Knudsen KA.Cadherin junctions in mammary tumors[J]Journal of mammary gland biology and neoplasia,2001,6(3):275-285.
[3]黄志勇,罗钒,陈孝平,等.黏附分子T-cadherin表达对C_6细胞恶性特性的影响[J].中华实验外科杂志,2005,22(10):1205-1206.
[4]Vestal DJ,Ranscht B.Glycosyl phosphatidylinositol-anchored T-cadherin mediates calcium-dependent,homophilic cell adhesion[J].J Cell Bioi,1992,119(2):451-461.[5]Phihppova M,Ivanov D,Tkachuk V,et al.Polarisation of T-cadherin to the leading edge of migrating vascular cells in vitro:a function in vascular cell motility?[J].Histochem Ceff Biol 2003,120:353-360.
[6]Sato M,Mori Y,Sakurada A,et al.The H-cadherin(CDHI3) gene is inactivated in human lung cancer[J].Hum Genet,l998,103(1):96-101.
[7]张志发,黄志勇,严群,等.T-cadherin分子在人肝细胞癌的表达及其与肝癌恶性生物学特征的关系[J].中华实验外科杂志,2008,25(7):829-830.
[8]Toyooka S,Toyooka KO,Harada K,et al,Aberrant methylation of the CDH13(H-cadherin) promoter region in colorectal cancers and adenomas[J].Cancer Res,2002,62(12):3382-3386.
[9]戴志慧,严群,李兆明,等.结直肠癌中T-cadherin分子表达异常及意义[J].华中科技大学学报·医学版,2008,37(1):121-122.
[10]Sun D,Zhang Z,Van do N,et al.Aberrant methylation of CDH13 gene in nasopharyngeal,carcinoma,could serveas a potential diagnostic biomarker[J].Oral Oncol,2007,43(1):82-87.
[11]Hibi K,Nakao A..Lymph node metastasis is infrequent in patients with highly-methylated colorectal cancer[J].Anticancer Res,2006,26(1A):55-58.
[12]Jones PA,Takai D.The role of DNA methylation in mammalian epigenetics[J].Science,2001,293(5532):1068-1070.
[13]Huang ZY,Wu Y,Hedrick N,et al.T-cadherin-mediated cell growth regulation involves G2 phase arrest and requires p21(CIP1/WAF1) expression[J]. Mol Cell Biol, 2003,23(2):566-578.
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[19] Takeuchi T, Liang SB, Matsuyoshi N, et al. Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma[J]. Lab Invest,2002,82 (8):1023-1029.
[20] Munro SB, Duclos AJ, Jackson AR, et al. Characterization of cadherins expressed by murine thymocytes[J]. Cell Immunol, 1996,169(2):309-312.
[21] Zhou S, Matsuyoshi N, Liang SB, et al, Expression of T-cadherin in Basal keratinocytes of skin[J].J Invest Dermatol,2002 ,118(6):1080-1184.
[22] Roller E, Ransch B. Differential targeting of T- and N-cadherin in polarized epithelial cells[J]. J Biol Chem, 1996,271(47):30061-30067.
[23] Ivanov D, Philippova M, Tkachuk V, et al. Cell adhesion molecule T-cadherin regulates vascular cell adhesion, phenotype and motility[J]. Exp Cell Res,2004, 293(2):207-218.
[24] Kipmen-Korgun D, Osibow K, Zoratti C, et al. T-cadherin mediates low-density lipoprotein-initiated cell proliferation via the Ca(2+)-tyrosine kinase-Erk1/2 pathway[J]. J Cardiovasc Pharmacol, 2005,45(5):418-430.
[25] Hug C, Wang J, Ahmad NS, et al, T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin[J].Proc Natl Acad Sci U S A,2004,101(28):10308-10313.
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[35]Marchio A,Meddeb M,Pineau P,et al.Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparati.ve genomic hybridization[J].Genes Chromosomes Cancer,1997,18:59-65.
[36]Riou P,Saffroy R,ComoyJ,et al.Investigation in liver tissues and cell lines of the transcription of 13 genes mapping to the 16q24 region that are frequently deleted in hepatocellular carcinoma[J].Clin Cancer Res,2002,8:3178-3186.
[37]Yu J,Ni M,Xu J,et al.Methytation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocelludar carcinog-enesis[J].BMC Cancer,2002,2:29.
[38]黄志勇,陈孝平,吴在德,等.黏附分子T-cadherin抑制C6胶质母细胞瘤增殖与p21表达相关[J].中华实验外科杂志,2007,22(11):1304-1305.
[39]Philippova M,Joshi MB,Kyriakakis E,et al.A guide and guard:the many faces of T-cadherin[J].Cell Signal,2009,21(7):1035-1044.
[40]Takeuchi T,Liang SB,Ohtsuki Y.Downregulation of expression of a novel cadherin molecule,T-cadherin,in basal cell carcinomaof the skin[J].Mol Carcinog,2002,35(4):173-179.
[41]Roman-Gomez J,Castillejo JA,Jimenez A,et al.Cadherin-13,a mediator of calcium -dependent cell-cell adhesion,is silenced by methtylation in chronic myetoid leukemia and correlates with pretreatment risk profile and cytogenetic response to interferon atfa[J].J Clin Oncol,2003,21(8):1472-1479.
[42]Hibi K,Koshikawa K,Inoue S,et al.Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer[J].Cancer Sci.2004,95(7):588-591.
[43]Sakai M,Ogama Y,Ouchida M,et al.Prevalent hyper-methylation of the CDH13gene promoter in malignant B cell lymphomas[J].Int J Oncol,2004,25(3):685-691.
[44]Widschwendter A,Ivarsson L,BlassnigA,et al.CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients[J].Int J Cancer,2004,109(2):163-1661
[45]于波,程滨珠,钟绮丽,等.皮肤基底细胞癌T钙黏蛋白的表达及其DNA异常甲基化分析[J].中华皮肤科杂志,2007,40(3):152-154.
[46]Lee SW.H-cadherin,a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer[J].Nature Med,1996,2(?):776-782.
[47]Miki Y,Katagiri T,Nakamura Y.Infrequent mutation of the H-cadherin gene on chromosome 16q24 in human breast cancers[J].Jpn J Cancer Res,1997,88(8):701-704.
[48]Takeuchi T,Misaki A,Chert BK,et al.H-cadherin expression in breast cancer[J].Histopathology.1999,35(1):87-88.
[49]Toyooka KO,Toyooka S,Virmani AK,et al.Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas[J]. Cancer Res, 2001,61 (11): 4556-4560.
[50] Ivanov D, Philippova M, Allenspach R, et al, T-cadherin upregulation correlates with cell-cycle progression and promotes proliferation of vascular cells[J]. Gardiovasc Res,2004,64(1)132-143.
[51] Widschwendter A, Ivarsson L, Blassnig A, et al. CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients[J]. Int J Cancer, 2004,109(2):163-166.
[52] Lewis CM, Cler LR, Bu DW, et al. Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk[J]. Clin Cancer Res, 2005, 11(1): 410-411.
[1]Huang ZY,Wu Y,Hedrick N,et al.T-cadherin-mediated cell growth regulation involves G2 phase arrest and requires p21(CIP1/WAF1) expression[J].Mol Cell BioI,2003,23(2):566-578.PMID:1250945S[PubMed-indexed for MEDLINE].
[2]Kemler R.Classical cadherins[J].Semin Cell Biol,1992,3(3):149-155.PMID:1623204[PubMed-indexed for MEDLINE].
[3] Koller E, Ransch B. Differential targeting of T- and N-cadherin in polarized epithelial cells[J]. J Biol Chem, 1996, 271 (47) :30061-30067. PMID: 8939953 [PubMed - indexed for MEDLINE].
[4] Vestal DJ, Ranscht B. Glycosyl phosphatidylinositol-anchored T-cadherin mediates calcium-dependent, homophilic cell adhesion[J].J Cell Biol, 1992,119(2):451-461. PMID: 1400585 [PubMed - indexed for MEDLINE].
[5] Kipmen-Korgun D, Osibow K, Zoratti C, et al. T-cadherin mediates low-density lipoprotein-initiated cell proliferation via the Ca(2+)-tyrosine kinase-Erk1/2 pathway[J]. J Cardiovasc Pharmacol, 2005, 45(5):418-430. PMID: 15821437 [PubMed -indexed for MEDLINE].
[6] Simonneau L, Gallego M, Pujol R. Comparative expression patterns of T-, N-, E-cadherins, beta-catenin, and polysialic acid neural cell adhesion molecule in rat cochlea during development: implications for the nature of Kolliker's organ [J]. J Comp Neurol, 2003,459(2):113-126. PMID: 12640664 [PubMed - indexed for MEDLINE].
[7] Takeuchi T, Liang SB, Matsuyoshi N, et al. Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma[J]. Lab Invest, 2002, 82(8):1023-1029. PMID: 12177241 [PubMed - indexed for MEDLINE].
[8] Munro SB, Duclos AJ, Jackson AR, et al. Characterization of cadherins expressed by murine thymocytes[J]. Cell Immunol, 1996,169(2):309-312. PMID: 8620560 [PubMed - indexed for MEDLINE].
[9] Zhou S, Matsuyoshi N, Liang SB, et al, Expression of T-cadherin in Basal keratinocytes of skin[J]. J Invest Dermatol, 2002 ,118(6): 1080-1184. PMID: 12060406 [PubMed -indexed for MEDLINE].
[10] Philippova M, Ivanov D, Tkachuk V, et al, Polarisation of T-cadherin to the leading edge of migrating vascular cells in vitro: a function in vascular cell motility? [J]. Histochem Cell Biol,2003,120(5):353-360. PMID: 14579115 [PubMed-indexed for MEDLINE].
[11] Hug C, Wang J, Ahmad NS, et al, T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin[J]. Proc Natl Acad Sci U S A,2004, 101 (28):10308-10313. PMID: 15210937 [PubMed - indexed for MEDLINE].
[12]Sato M,Mori Y,Sakurada A,et al,The H-cadherin(CDH13) gene is inactivated in human lung cancer[]].Hum Genet,1998,103(1):96-101.PMID:9737784[PubMed -indexed for MEDLINE].
[13]Toyooka S,Toyooka KO,Harada K,et al,Aberrant methylation of the CDH13(H-cadherin) promoter region in colorectal cancers and adenomas[J].Cancer Res,2002,62(12):3382-3386.PMID:12067979[PubMed - indexed for MEDLINE].
[14]戴志慧,严群,李兆明,等.结直肠癌中T-cadherin分子表达异常及意义[J].华中科技大学学报·医学版,2008,37(1):121-122.
[15]Sun D,Zhang Z,Van do N,et al.Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker[J].Oral 0ncoi,2007,43(1):82-87.PMID:16807071[PubMed - indexed for MEDLINE].
[16]Hibi K,Nakao A.Lymph node metastasis is infrequent in patients with highly-methylated colorectal cancer[J].Anticancer Res,2006,26(1A):55-58 PMID:16475679[PubMed - indexed for MEDLINE].
[17]Jones PA,Takai D.The role of DNA methylation in mammalian epigenetics[J].Science,2001,293(5532):1068-1070.PMID:11498573[PubMed - indexed for MEDLINE].
[18]Takeuchi T,Misaki A,Liang SB,et al.Expression of T-cadherin(CDH13,H-Cadherin) in human brain and its characteristics as a negative growth regulator of epidermal growth factor in neuroblastoma cells[J].J Neurochem,2000,74(4):1489-1497.PMID:10737605[PubMed - indexed for MEDLINE].
[19]Lee SW,Reimer CL,Campbell DB,et al.H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo[J].Carcinogenesis,1998,19(6):1157-1159.PMID:9667758[PubMed - indexed for MEDLINE].
[20]梁治坤,黄志勇,陈孝平,等。5-杂氮-2′-脱氧胞苷诱导裸鼠HepG2种植瘤细胞T-cadherin的表达及其对种植瘤的抑制作用[J].世界华人消化杂志,2008,16(16):1741-1745.
[21]Ivanov D,Philippova M,Allenspach R,et al.T-cadherin upregulation correlates with cell-cycle progression and promotes proliferation of vascular cells[J].Cardiovasc Res,2004,64(I):132-43.PMID:15364621[PubMed - indexed for MEDLINE].