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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,同时这些病例均存在癌细胞分化差,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
Disregulation of the cell cycle is an early event in breast cancer and the G1 phase involving cyclinD1 and p16 cyclin is aberrant in most breast cancers. CyclinD1 protein expression and gene amplification were found in normal breast tissues, benign cancers with high risk of canceration, invasive carcinomas, and were higher with almost atypical hyperplasia of cells and almost close to invasive carcinomas. CyclinD1 and cancer infiltration. There was no significant difference in CyclinD1 protein expression between benign and non-cancerous benign diseases and later benign cancers. Overexpression of CyclinD1 may up-regulate p21 and arrest the growth of cancer tissue. In human breast cancer cell lines, 17-β-estradiol induces CyclinD1 expression, multiple promoter elements may play an important role, and the interaction of ERα and Sp1 proteins at these sites has been demonstrated. The low expression of CyclinD1 in breast cancer tissues is highly consistent with the negative expression of estrogen receptor. Patients with overexpression of CyclinD1 have poor response to progestin. CyclinD1 plays an important role in many oncogene regulatory pathways, and it is necessary to give anti-CyclinD1 treatment to breast cancer patients with active neu-ras pathway. p16 is a novel tumor suppressor gene. It has been found that the deletion and mutation of p16 exist in breast cancer cell lines. The loss of heterozygosity in 9p21 region exists in breast cancer tissues, but p16 gene protein is not expressed in more than half of cases, meanwhile, these All cases had poor differentiation of cancer cells, negative expression of ER and PgR and overexpression of p53, which may be due to the transcriptional changes of p16 gene. Hypermethylation of p16 gene is the main reason for the loss of p16 mRNA and protein expression. p16 mRNA expression and patient age, tumor size, ER, PgR