Courjal F, Louason G, Speiser P, Katsaros D, Zeillinger R, Theillet C
Institut de Biologie Moléculaire, UMR 9942, CNRS 1919, Montpellier, France.
Int J Cancer. 1996 Aug 22;69(4):247-53. doi: 10.1002/(SICI)1097-0215(19960822)69:4<247::AID-IJC1>3.0.CO;2-X.
Evidence of the involvement of cyclin genes in genetic alterations in human cancer is growing. In the present study, we investigated the amplification, in human breast and ovarian cancer, of 5 cyclin genes; cyclin A, cyclin D1, cyclin D2, cyclin D3 and cyclin E. For this purpose, a series of 1,171 breast and 237 ovarian tumors tested for DNA amplification by Southern blotting and a subset of 132 breast and 22 ovarian cancers were analyzed for RNA expression levels by slot-blot and Northern blotting. In breast tumors, only cyclin D1 was found to be activated in a sizeable fraction of the tumors (amplification 12.6%, overexpression 19%). Cyclin A, D2, D3, and E genes never, or only on rare occasions, showed increased DNA copy numbers and were never found overexpressed at the RNA level. Amplification of cyclin D1 correlated with ER+ breast cancer and the presence of lymph-node metastasis. Interestingly, we were also able to determine an association with invasive lobular carcinoma. Our data suggest that cyclin D1 activation determines the evolution of a particular subset of estrogen-responsive tumors. Data obtained in ovarian tumors contrasted with observations in breast cancer. Cyclin D1 DNA amplification was much less frequent in ovarian than in breast tumors (3.3% vs. 12.6%), whereas cyclin E amplification and overexpression were observed in a significant number of cases (12.5% and 18.0% respectively). Cyclin A, cyclin D2 and D3 rarely showed anomalies at the DNA level and were never overexpressed. No clear correlation could be observed between amplification of the cyclin E gene and tumor type, stage or grade in ovarian cancer. Data presented here suggest distinct pathways of cyclin activation in human breast and ovarian cancer.
细胞周期蛋白基因参与人类癌症基因改变的证据越来越多。在本研究中，我们调查了5种细胞周期蛋白基因（细胞周期蛋白A、细胞周期蛋白D1、细胞周期蛋白D2、细胞周期蛋白D3和细胞周期蛋白E）在人类乳腺癌和卵巢癌中的扩增情况。为此，通过Southern印迹法对1171例乳腺癌和237例卵巢肿瘤进行了DNA扩增检测，并通过狭缝印迹法和Northern印迹法对132例乳腺癌和22例卵巢癌的一个子集进行了RNA表达水平分析。在乳腺肿瘤中，仅发现相当一部分肿瘤中的细胞周期蛋白D1被激活（扩增率为12.6%，过表达率为19%）。细胞周期蛋白A、D2、D3和E基因从未或仅在极少数情况下显示DNA拷贝数增加，且从未在RNA水平上发现过表达。细胞周期蛋白D1的扩增与雌激素受体阳性乳腺癌以及淋巴结转移的存在相关。有趣的是，我们还能够确定其与浸润性小叶癌的关联。我们的数据表明，细胞周期蛋白D1的激活决定了雌激素反应性肿瘤特定亚群的演变。在卵巢肿瘤中获得的数据与乳腺癌的观察结果形成对比。细胞周期蛋白D1的DNA扩增在卵巢肿瘤中比在乳腺肿瘤中少见得多（3.3%对12.6%），而在相当数量的病例中观察到细胞周期蛋白E的扩增和过表达（分别为12.5%和18.0%）。细胞周期蛋白A、细胞周期蛋白D2和D3在DNA水平上很少显示异常，且从未过表达。在卵巢癌中，细胞周期蛋白E基因的扩增与肿瘤类型、分期或分级之间未观察到明显的相关性。此处呈现的数据表明，人类乳腺癌和卵巢癌中细胞周期蛋白激活的途径不同。
