The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer.
The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer.
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DOI：
10.1186/bcr3376
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发表时间：
2013-01-21
期刊：
影响因子：
--
通讯作者：
Jukkola-Vuorinen A
中科院分区：
文献类型：
--
作者：
Peurala E;Koivunen P;Haapasaari KM;Bloigu R;Jukkola-Vuorinen A
视网膜母细胞瘤蛋白肿瘤抑制基因（RB）编码一种调节细胞周期的核磷酸化蛋白的缺失在许多人类癌症中被发现，并可能导致p16-cyclin D1-CDK4/6-RB通路的破坏。已知Cyclin D1激活CDK4，然后使RB蛋白磷酸化，导致细胞周期的进展。p16抑制CDK4，保持RB低磷酸化，阻止细胞周期进展。然而，细胞周期蛋白D1、CDK4和p16这三种标志物在乳腺癌和癌变中的意义仍存在争议。材料由102个福尔马林固定的人乳腺癌样本组成，免疫组织化学方法评估细胞周期蛋白D1、CDK4和p16的表达。实时荧光定量PCR检测细胞周期蛋白D1 mRNA表达量。cyclin D1高表达与乳腺肿瘤分级降低、雌激素、孕激素受体阳性、增殖活性降低、乳腺癌特异性生存期和总生存期升高有统计学意义。细胞周期蛋白D1高表达的肿瘤细胞周期蛋白D1 mRNA表达量高1.8倍。CDK4表达与细胞周期蛋白D1表达或生存数据无关。p16表达与人表皮生长因子受体2 （HER2）阴性相关，并增加乳腺癌特异性生存期和无病生存期。cyclin D1、CDK4与p16之间无统计学相关性。Cyclin D1与良好的乳腺癌预后相关，但其功能独立于CDK4。高cyclin D1表达可能部分归因于CCND1转录增加。p16与更好的预后相关，并且可能在没有CDK4的情况下发挥作用。综上所述，细胞周期蛋白D1、CDK4和p16似乎在人类乳腺癌中独立起作用。
Loss of the retinoblastoma protein tumor suppressor gene (RB) coding for a nuclear phosphoprotein that regulates the cell cycle is found in many human cancers and probably leads to disruption of the p16-cyclin D1-CDK4/6-RB pathway. Cyclin D1 is known to activate CDK4, which then phosphorylates the RB protein, leading to cell cycle progression. p16 inhibits CDK4, keeping RB hypophosphorylated and preventing cell cycle progression. The significance of these three markers, cyclin D1, CDK4 and p16, for breast cancer and carcinogenesis is nevertheless still controversial. The material consisted of 102 formalin-fixed human breast cancer samples, in which cyclin D1, CDK4 and p16 expression was evaluated immunohistochemically. The amounts of cyclin D1 mRNA present were analyzed by quantitative real time PCR. High cyclin D1 expression statistically significantly correlated with lower tumor grade, estrogen and progesterone receptor positivity and lower proliferation activity in breast tumors and increased breast cancer-specific survival and overall survival. Tumors with high cyclin D1 protein had 1.8 times higher expression of cyclin D1 mRNA. CDK4 expression did not correlate with cyclin D1 expression or the survival data. p16 expression was associated with Human Epidermal Growth Factor Receptor 2 (HER2) negativity and increased breast cancer-specific survival and disease-free survival. No statistical correlations between cyclin D1, CDK4 and p16 were found. Cyclin D1 was associated with a good breast cancer prognosis but functioned independently of CDK4. High cyclin D1 expression may be partially due to increased CCND1 transcription. p16 correlated with a better prognosis and may function without CDK4. In conclusion, it appears that cyclin D1, CDK4 and p16 function independently in human breast cancer.
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影响因子：
1.8
作者：
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通讯作者：
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影响因子：
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影响因子：
64.5
作者：
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影响因子：
4.3
作者：
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