Aberrant cytoplasmic expression of the p16 protein in breast cancer is associated with accelerated tumour proliferation.
Aberrant cytoplasmic expression of the p16 protein in breast cancer is associated with accelerated tumour proliferation.
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乳腺癌中p16蛋白的异常细胞质表达与加速肿瘤增殖有关。
DOI：
10.1038/bjc.1998.739
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发表时间：
1998-12
影响因子：
8.8
通讯作者：
Sinn, HP
中科院分区：
文献类型：
--
作者：
Emig, R;Magener, A;Ehemann, V;Meyer, A;Stilgenbauer, F;Volkmann, M;Wallwiener, D;Sinn, HP
p16蛋白在细胞进入细胞周期G1期的过程中起重要作用。我们研究了p16蛋白在368例侵袭性和52例非侵袭性恶性肿瘤中的表达，以及88例局部复发肿瘤和3种肿瘤细胞系中的表达。利用单克隆和多克隆抗P16抗体和肿瘤细胞悬液的免疫印迹法，在石蜡切片上检测P16蛋白的表达。对肿瘤细胞株进行聚合酶链反应-单链多态性（PCR-SSCP）分析和直接DNA测序。将结果与已建立的预后参数、DNA流式细胞术和p53蛋白表达进行比较。在33例（9%）浸润性癌和2例（4%）导管内癌中，可见p16蛋白的细胞质积累。这些病例的特点是组织学分化程度差，雌激素受体和孕激素受体缺失，p53蛋白频繁过表达。此外，p16异常表达的乳腺癌表现出高增殖活性，s期的中位数分数比对照组高74%，Ki67的中位数分数升高到75%。应用PCR-SSCP和直接DNA测序，在三个细胞质表达p16的细胞系中未检测到p16基因的遗传改变。这些结果表明，细胞质中p16蛋白的积累识别了一个具有加速肿瘤增殖和其他不利参数的高度恶性乳腺癌亚群。所描述的蛋白质积累显然不是由p16基因的改变引起的。
The p16 protein plays an important role in the transition of cells into the G1 phase of the cell cycle. We have studied the prevalence of p16 protein expression in breast carcinomas in a prospective series of 368 invasive and 52 non-invasive malignancies, as well as in 88 locally recurring tumours and three tumour cell lines. p16 protein expression was evaluated immunohistochemically on paraffin sections using monoclonal and polyclonal anti-p16 antibodies, and by immunoblotting of tumour cell suspensions. Tumour cell lines were also subjected to polymerase chain reaction-single strand polymorphism (PCR-SSCP) analysis and direct DNA sequencing. The results were compared with established prognostic parameters, DNA flow cytometry and p53 protein expression. In 33 (9%) invasive and two (4%) intraductal carcinomas, a cytoplasmic accumulation of the p16 protein was seen. These cases were characterized by poor histological grade of differentiation, loss of of oestrogen receptors and progesterone receptors and frequent overexpression of the p53 protein. In addition, breast carcinomas with aberrant p16 expression demonstrated a high proliferative activity, with median S-phase fractions 74% higher than in the control group and the median Ki67 fractions elevated to 75%. A genetic alteration of the p16 gene was not detectable in three analysed cell lines with cytoplasmic p16 expression applying PCR-SSCP and direct DNA sequencing. These results indicate that cytoplasmic accumulation of the p16 protein identifies a subset of highly malignant breast carcinomas with accelerated tumour proliferation and other unfavourable parameters in breast cancer. The described protein accumulation is apparently not caused by an alteration of the p16 gene.
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影响因子：
6.4
作者：
FEICHTER, GE;MUELLER, A;GOERTTLER, K
通讯作者：
GOERTTLER, K
影响因子：
64.8
作者：
KOH, J;ENDERS, GH;HARLOW, E
通讯作者：
HARLOW, E
影响因子：
3.3
作者：
CHARPIN, C;DEVICTOR, B;PIANA, L
通讯作者：
PIANA, L
DOI：
10.1016/0304-419x(93)90021-4
发表时间：
1993-05-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
GOODRICH, DW;LEE, WH
通讯作者：
LEE, WH
DOI：
10.1093/jnci/85.3.200
发表时间：
1993-02-03
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
ALLRED, DC;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL