首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status.
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Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status.

机译:人乳腺癌中Cyclin D1和视网膜母细胞瘤基因表达:与肿瘤增殖和雌激素受体状态的关系。

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Cyclin D1 (CCND1) and retinoblastoma (Rb) genes are cell cycle regulators which are altered in some breast carcinomas. However, the possible cooperation between CCND1 and Rb, as well as the influence and coincidence of their abnormalities in the proliferative capacity of mammary carcinoma cells in vivo, is still unknown. In order to assess both the significance of the CCND1 gene and Rb alterations in breast carcinomas and their relationship with the proliferative capacity of the tumours and other clinico-pathological factors, CCND1 mRNA expression was studied in 46 cases of primary breast carcinomas and matched normal tissue, 45 of which were also studied immunohistochemically, Rb expression was analysed in the same cases by immunohistochemistry, whereas the proliferative activity of the carcinoma was evaluated by flow cytometry. CCND1 mRNA was overexpressed in 19 tumours (41 per cent). Sixteen cases showed diffuse immunohistochemical expression, ten carcinomas had few positive cells, and 19 were absolutely negative. CCND1 mRNA and protein overexpression was associated with oestrogen receptor (ER) expression by the tumour. Interestingly, lack of ER expression was associated with a decreased CCND1 mRNA signal in non-overexpressed tumours. No association was observed between CCND1 mRNA or protein overexpression and tumour proliferation or other clinico-pathological parameters. Loss of Rb expression was observed in 26 per cent of the tumours. This abnormality was significantly associated with increased mean S-phase (P = 0.017) and decreased CCND1 mRNA expression in non-overexpressed tumours, supporting in vivo the postulated regulatory loop between Rb and CCND1 in vitro. We conclude that CCND1 up-regulation is not associated with increased proliferative activity in breast carcinomas, whereas its expression might be regulated in vivo by hormones and Rb. Loss of Rb expression is significantly associated with an increased proliferation of tumour cells, suggesting an important role in the progression of a subset of breast carcinomas, regardless of CCND1 abnormalities.
机译:细胞周期蛋白D1(CCND1)和成视网膜细胞瘤(Rb)基因是细胞周期调节因子,在某些乳腺癌中会发生改变。然而,CCND1和Rb之间可能的合作,以及它们在体内对乳腺癌细胞增殖能力的影响的影响和巧合仍是未知的。为了评估CCND1基因和Rb改变在乳腺癌中的意义及其与肿瘤增殖能力和其他临床病理因素的关系,研究了46例原发性乳腺癌和匹配的正常组织中CCND1 mRNA的表达。 ,其中45个也进行了免疫组织化学研究,在同一病例中通过免疫组织化学分析了Rb的表达,而流式细胞术则评估了癌细胞的增殖活性。 CCND1 mRNA在19个肿瘤中过表达(41%)。 16例表现出弥漫性免疫组织化学表达,10例癌的阳性细胞很少,19例绝对阴性。 CCND1 mRNA和蛋白的过度表达与肿瘤引起的雌激素受体(ER)表达有关。有趣的是,在非过度表达的肿瘤中,ER表达的缺乏与CCND1 mRNA信号的降低有关。 CCND1 mRNA或蛋白质的过表达与肿瘤增殖或其他临床病理参数之间未发现关联。在26%的肿瘤中观察到Rb表达的丧失。这种异常与平均S期增加(P = 0.017)和CCND1 mRNA在未过度表达的肿瘤中的表达显着相关,在体内支持Rb和CCND1在体外的假定调节环。我们得出的结论是CCND1的上调与乳腺癌的增殖活性增加无关,而CCND1的表达可能在体内受到激素和Rb的调节。 Rb表达的丧失与肿瘤细胞增殖的增加显着相关,这提示无论CCND1异常如何,在乳腺癌子集的进展中都起着重要作用。

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