Cyclin D1与乳腺癌相关性研究进展

Cyclin D1在正常乳腺形成过程中起重要作用，亦与乳腺癌发生、发展过程密切相关。其过表达能缩短G1期，促使细胞提前进入S期，引起细胞生长失控、转化和癌变。Cyclin D1在多个癌基因调控通路上有重要作用，对Neu—Ras通路激活的乳腺癌患者，有必要给予抗cyclin D1治疗。同时，Cyclin D1在乳腺癌中的表达情况有助于乳腺癌的分期、分级以及治疗方案的选择和预后的判断。现将Cyclin D1与乳腺癌相关性研究进展情况予以综述。     

Cyclin D1与恶性肿瘤

Cyclin D1 (CD1 )是一种作用于 G1期的细胞周期相关蛋白 ,与多种蛋白相互作用促进细胞进入 S期。CD1基因是一种弱致癌基因 ,可与多种癌基因协同促进细胞转化。在多种肿瘤中有 CD1基因扩增和 /或表达增强 ,其临床意义与肿瘤类型有关。用CD1反义基因体外转染人类肿瘤细胞可抑制肿瘤细胞增殖、降低其致瘤性。一、CD1的生物学特性细胞周期素 (cyclin)是一与细胞周期相关的核蛋白家族 ,其中细胞周期素 D1 (cyclin D1 ,CD1 )与G1期相关 ,分子量 36k D。CD1与细胞周期素依赖激酶 4和 6(Cyclin dependent kinase4and6,cdk4和cdk6)形成复合…     

乳腺癌预后分子标记物研究进展

乳腺癌患者预后受诸多因素的影响。正确选择乳腺癌预后标记物对研究乳腺癌的生物学行为、指导系统综合治疗具有重要意义。现综述乳腺癌预后相关分子标记物的研究进展，评价其在乳腺癌治疗、预后等方面中的潜在应用。     

乳腺癌预后的分子标志物研究进展

准确判断乳腺癌的预后有利于临床疗效评价。目前乳腺癌预后相关的分子标志物研究已成为一个热点，现就此领域的研究现状及最新进展作一综述。     

乳腺癌相关DNA甲基化生物标记的研究进展

乳腺癌是常见的女性恶性肿瘤。据估计2002年全球每年新发病例115万（占所有新发癌症病例数的23％）,已成为除肺癌外最常见的恶性肿瘤。表观遗传改变被证明在乳腺癌的发生、发展中起着至关重要的作用心,其留下的可以被检测的表观遗传痕迹（尤其是DNA的甲基化）为乳腺癌的早期诊断和临床治疗反应及预后评价带来有价值的应用前景。     

乳腺癌微转移标记物研究进展

骨髓、淋巴结微转移的检出率与乳腺癌患者的预后密切相关,并已成为重要的独立预后因素,可早期诊断肿瘤复发和远处转移。目前乳腺癌微转移标记物的研究主要集中在乳腺小黏蛋白、人乳腺珠蛋白（hMAM）、黏蛋白1、丝氨酸蛋白酶抑制因子（maspin）、细胞角蛋白（CK）19等。     

CyclinD1、p16与乳腺癌相关性的研究进展

细胞周期的失调控在乳腺癌中是一早期事件，涉及细胞周期素CyclinD1和p16的G1期在大多数乳腺癌中出现异常。在正常乳腺组织、癌变危险性大的良性疾病、浸润性癌中均发现了CyclinD1蛋白表达和基因扩增，且在有细胞不典型增生的情况下较高，几乎接近浸润性癌。CyclinD1和癌的浸润性有关。CyclinD1蛋白表达在未癌变的良性疾病和以后癌变的良性疾病之间并无显著性差异。CyclinD1过表达有可能上调p21而使癌组织生长停滞。在人类乳腺癌细胞株，17－β雌二醇可诱导CyclinD1表达，可能有多个启动子元件发挥了重要作用，ERα和Sp1蛋白在这些位点的相互作用已被证实。乳腺癌组织中CyclinD1低表达与雌激素受体阴性表达高度一致。CyclinD1过度表达病人对孕激素治疗效果差。CyclinD1在多个癌基因调控通路上有重要作用，对有激活的neu-ras通路的乳腺癌病人，有必要给予抗CyclinD1治疗。p16是一种新型肿瘤抑制基因，已发现其缺失及突变存在于乳腺癌细胞株，9p21区的杂和性丢失存在于乳腺癌组织中，但p16基因蛋白在半数以上的病例不表达，同时这些病例增存在癌细胞分化差，ER和PgR阴性表达，p53过表达，这可能由于p16基因在转录水平的改变。p16基因的高甲基化是p16mRNA和蛋白失表达的主要原因。p16mRNA表达与病人年龄、肿瘤大小、ER、PgR无关。p16高表达的病人对激素的反应必低。p16在乳腺癌的基因治疗中有潜在的利用价值。     

乳腺癌微转移标记物研究进展

骨髓、淋巴结微转移的检出率与乳腺癌患者的预后密切相关,并已成为重要的独立预后因素,可早期诊断肿瘤复发和远处转移。目前乳腺癌微转移标记物的研究主要集中在乳腺小黏蛋白、人乳腺珠蛋白(hMAM)、黏蛋白1、丝氨酸蛋白酶抑制因子(maspin)、细胞角蛋白(CK)19等。     

乳腺癌预后分子标记物研究进展

乳腺癌患者预后受诸多因素的影响.正确选择乳腺癌预后标记物对研究乳腺癌的生物学行为、指导系统综合治疗具有重要意义.现综述乳腺癌预后相关分子标记物的研究进展,评价其在乳腺癌治疗、预后等方面中的潜在应用.     

AIB1在乳腺癌中的研究进展

国外研究表明乳腺癌扩增性抗原1(amplified in breast cancer 1,AIB1)与乳腺癌的发生、发展、乳腺癌内分泌治疗耐药及不良预后关系密切,即过度表达的AIB1与表皮生长因子受体家族(HER2)共同降低内分泌治疗效果及无病生存期。AIB1在乳腺癌内分泌治疗耐药机制中的作用及临床上克服内分泌治疗耐药方法有待进一步研究。AIB1有可能是内分泌治疗耐药预测指标和乳腺癌抗肿瘤治疗靶点。     

Cyclin D1 and prognosis in human breast cancer

We have used immunohistochemical staining to assess the expression of cyclin D1 in formalin-fixed sections of 345 breast carcinomas, dating back 20 years. Clinical follow-up data were available on all patients. Approximately 50% of the tumours showed excessive nuclear staining for cyclin D1 as compared with normal epithelium. Some tumours showed strong cytoplasmic staining in the absence of nuclear staining, and around 25% of the tumours were judged to be negative for nuclear cyclin D1. Contrary to expectations, moderate/strong staining for cyclin D1 was associated with improved relapse-free and overall survival relative to patients whose tumours stained weakly or negatively. Conversely, tumours that were considered negative for cyclin D1 staining had an adverse prognosis, and the poor outcome was further accentuated if the tumours were also oestrogen receptor-negative. A possible explanation for our findings is that tumours in which cyclin D1 levels are abnormally low may have sustained mutations in other genes, such as RB1 and that it is this abnormality that has the more significant impact on survival from breast cancer. © 1996 Wiley-Liss, Inc.     

Cyclin D1 in breast cancer pathogenesis.

Taking a perspective on available evidence that emphasizes relevance to human disease, cyclin D1 is solidly established as an oncogene with an important pathogenetic role in breast cancer and other human tumors. However, the precise cellular mechanisms through which aberrant cyclin D1 expression drives human neoplasia are less well established. Indeed, emerging evidence suggests that cyclin D1 might act, predominantly or at least in part, through pathways that do not involve its widely accepted function as a cell cycle regulator. Although therapeutic exploitation of the role of cyclin D1 as a molecular driver of breast cancer carries great promise, it is also suggested that direct targeting of the cyclin D1 gene or gene products may prove more successful than approaches that rely on arguably incomplete knowledge of the oncogenic mechanisms of cyclin D1.     

细胞周期素D1与肺癌研究进展

细胞周期素D1(CyclinD1)在细胞周期的正常调控中鹱殴丶饔?近期研究发现,破在肺癌发病过程中CyclinD1基因表达失衡有不同的分子生物学机制,其表达增高的部位、水平、和方式均有重要特点.现综述CyclinD1与肺癌研究的最新进展.     

Cyclin D1 protein expression and function in human breast cancer

Cyclin D1 is a cell-cycle regulator essential for G₁, phase progression and a candidate proto-oncogene implicated in pathogenesis of several human tumour types, including breast carcinomas. In spite of the accumulating genetic evidence, however, there are no data regarding abundance and properties of the cyclin D1 protein in breast cancer. We now report aberrant nuclear overexpression/accumulation of the cyclin D1 protein in about half of the 170 primary breast carcinoma specimens analyzed by monoclonal antibody immunohistochemistry, indicating that the frequency of cyclin D1 abnormalities may be considerably higher than previously deduced from DNA amplification studies. A comparison of the expression patterns in matched lesions at different stages of tumour progression revealed that the cyclin D1 protein aberration appears to reflect a relatively early event and that, when acquired by a tumour, it is maintained throughout breast cancer progression including metastatic spread. In both tumour tissues and breast cancer cell lines, the abundance of this protein shows characteristic variations consistent with a cell-cycle oscillation and the peak levels expressed in G₁. In all 7 cell lines whose retinoblastoma (Rb) protein is mutant or complexed to SV40 T antigen, exceptionally low levels of cyclin D1 protein and mRNA were found. Antibody-mediated and anti-sense oligonucleotide knockout experiments demonstrate the requirement for the cell-cycle regulatory function of cyclin D1 in breast cancer lines with single or multiple copies of the gene and reveal the absence of such a requirement in the cell lines with Rb defects. Our data are consistent with the notion that the emerging “Rb-cyclin D1 pathway” represents a frequent target of oncogenic abnormalities in breast cancer. © 1994 Wiley-Liss, Inc.     

胰腺癌组织中cyclin D1和rasp21表达的研究

目的 :探讨细胞周期素 (cyclin)D1和rasp2 1蛋白在胰腺癌中的相互关系。方法 :应用免疫组化方法检测cyclinD1和rasp2 1在胰腺癌中的表达。结果 :cyclinD1和rasp2 1在胰腺癌中的阳性表达率分别为60 0 %和 72 5 % ,二者在胰腺癌中的表达差异有统计学意义 ,P <0 0 5。cyclinD1阳性表达与肿瘤的分化程度密切相关 ,P <0 0 5。结论 :cyclinD1和rasp2 1过表达在胰腺癌发生过程中具有协同作用。     

基质金属蛋白酶与乳腺癌关系研究进展

细胞外基质(ECM)的降解是肿瘤侵袭、转移的重要信号和途径.基质金属蛋白酶(MMP)是溶解ECM的一组酶类,金属蛋白酶组织抑制物(TIMP)是MMP的特异性抑制物.二者的表达及代谢失衡与乳腺癌的侵袭、转移和临床预后有密切联系.TIMP有望成为新的抗乳腺癌临床用药.现综述近年来有关MMP、TIMP与乳腺癌关系的研究进展.     

Cyclin D1 overexpression is more prevalent in non-Caucasian breast cancer

African-American women with breast cancer consistently show a shortened survival when compared with Caucasians with breast cancer, however it is not clear whether this is due to socioeconomic factors or to racial differences in tumor biology. Cyclin D1 overexpression has been demonstrated in 60-80% of female breast cancers, however these studies have not included race or ethnicity data. We examined the level of cyclin D1 protein expression in 139 cases of female breast cancer obtained from different ethnic populations. Using an immunoperoxidase-based technique and a polyclonal anti-cyclin D1 antibody, the rate of overexpression was 68%. Cyclin D1 overexpression tended to be more frequent in cases from non-Caucasian patients when compared with those from Caucasian patients (77% vs. 59%, p=0.051). Our findings suggest that non-Caucasian ethnicity may be important in predicting cyclin D1 overexpression. Cyclin D1 could therefore serve as a possible target in managing breast cancer in the African-American population.