Bechtel P E, Hickey R J, Schnaper L, Sekowski J W, Long B J, Freund R, Liu N, Rodriguez-Valenzuela C, Malkas L H
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201, USA.
Cancer Res. 1998 Aug 1;58(15):3264-9.
Despite extensive research efforts to identify unique molecular alterations in breast cancer, to date, no characteristic has emerged that correlates exclusively with malignancy. Recently, it has been shown that the multiprotein DNA replication complex (synthesome) from breast cancer cells has a significantly decreased replication fidelity compared to that of nonmalignant breast cells. Proliferating cell nuclear antigen (PCNA) functions in DNA replication and DNA repair and is a component of the synthesome. Using two-dimensional PAGE analysis, we have identified a novel form of PCNA in malignant breast cells. This unique form is not the result of a genetic alteration, as demonstrated by DNA sequence analysis of the PCNA gene from malignant and nonmalignant breast cells. This novel form is most likely the result of an alteration in the post-translational modification of PCNA in malignant breast cells. These findings are significant in that it is now possible to link changes in the fidelity of DNA replication with a specific alteration of a component of the DNA synthetic apparatus of breast cancer cells. The novel form of PCNA may prove to be a new signature for malignant breast cells.
尽管为识别乳腺癌中独特的分子改变进行了广泛的研究，但迄今为止，尚未出现仅与恶性肿瘤相关的特征。最近研究表明，与非恶性乳腺细胞相比，乳腺癌细胞中的多蛋白DNA复制复合体（合成体）的复制保真度显著降低。增殖细胞核抗原（PCNA）在DNA复制和DNA修复中发挥作用，是合成体的一个组成部分。通过二维聚丙烯酰胺凝胶电泳分析，我们在恶性乳腺细胞中鉴定出一种新型PCNA。如对恶性和非恶性乳腺细胞的PCNA基因进行DNA序列分析所示，这种独特形式并非基因改变的结果。这种新型形式很可能是恶性乳腺细胞中PCNA翻译后修饰改变的结果。这些发现意义重大，因为现在有可能将DNA复制保真度的变化与乳腺癌细胞DNA合成装置的一个组成部分的特定改变联系起来。新型PCNA可能被证明是恶性乳腺细胞的一个新标志。
