Mrhalová M, Kodet R, Strnad P
Ustav patologie a molekulární medicíny 2. LF UK a FNM, Praha.
Cas Lek Cesk. 2002 Nov 8;141(22):708-14.
Overexpression of oncogenic proteins may be caused by gene amplifications. Cyclin D1 participates in regulation of the cell cycle. Relations between cyclin D1 expression and amplification of CCND1 gene encoding this protein in invasive duct breast carcinomas (IDC) are not fully elucidated. An increased interest is also focused on relations to the estrogen receptor (ER alpha).
We investigated copy numbers of the CCND1 gene, expression of cyclin D1 and expression of ER alpha in a group of 60 females and 1 male with IDC. The age range varied from 33 to 89 years (median 57 years). The number of CCND1 gene copies and the number of chromosome 11 was evaluated using FISH, the expression of cyclin D1 and ER alpha was investigated by IHC. We detected a strong amplification of CCND1 gene (> 10 copies per tumor cell nuclei) in 9 patients, weak amplification (< or = copies) in 16 patients. Amplification of the CCND1 gene correlated well with the overexpression of cyclin D1. We observed the overexpression of cyclin D1 also in 13 of 36 patients without the gene amplification; therefore, the mechanism of the protein overexpression is different than that caused by the gene amplification in a proportion of patients. Amplification of the CCND1 gene was associated with a high histologic grade of IDC, whereas cases with cyclin D1 overexpression only were not. 24 of 31 patients with overexpression of cyclin D1 coexpressed ER alpha. We did not find correlation between expression/amplification of cyclin D1/CCND1 gene and the size of carcinomas and with metastases to the axillary lymph nodes.
Amplification of the CCND1 gene is associated with overexpression of cyclin D1 in a majority of IDC. Overexpression of cyclin D1 is related to an increased expression of ER alpha. Interaction between cyclin D1 and ER alpha may explain low response to anti-estrogen therapy of some patients.
致癌蛋白的过表达可能由基因扩增引起。细胞周期蛋白D1参与细胞周期的调控。浸润性导管乳腺癌（IDC）中细胞周期蛋白D1的表达与编码该蛋白的CCND1基因扩增之间的关系尚未完全阐明。人们也越来越关注其与雌激素受体（ERα）的关系。
我们调查了60名女性和1名男性IDC患者中CCND1基因的拷贝数、细胞周期蛋白D1的表达以及ERα的表达。年龄范围为33至89岁（中位数57岁）。使用荧光原位杂交（FISH）评估CCND1基因的拷贝数和11号染色体的数量，通过免疫组织化学（IHC）研究细胞周期蛋白D1和ERα的表达。我们在9例患者中检测到CCND1基因的强烈扩增（每个肿瘤细胞核>10个拷贝），16例患者中检测到微弱扩增（≤拷贝）。CCND1基因的扩增与细胞周期蛋白D1的过表达密切相关。我们还在36例无基因扩增的患者中的13例中观察到细胞周期蛋白D1的过表达；因此，在一部分患者中，蛋白质过表达的机制与基因扩增引起的机制不同。CCND1基因的扩增与IDC的高组织学分级相关，而仅细胞周期蛋白D1过表达的病例则不然。31例细胞周期蛋白D1过表达的患者中有24例共表达ERα。我们未发现细胞周期蛋白D1/CCND1基因的表达/扩增与癌肿大小以及腋窝淋巴结转移之间存在相关性。
在大多数IDC中，CCND1基因的扩增与细胞周期蛋白D1的过表达相关。细胞周期蛋白D1的过表达与ERα表达增加有关。细胞周期蛋白D1与ERα之间的相互作用可能解释了一些患者对抗雌激素治疗反应较低的原因。
