Rochlitz C F, Scott G K, Dodson J M, Liu E, Dollbaum C, Smith H S, Benz C C
Cancer Research Institute, University of California, San Francisco 94143.
Cancer Res. 1989 Jan 15;49(2):357-60.
To test the hypothesis that ras activation is involved in the final stages of breast cancer progression, we analyzed tumor DNA derived from 60 different patients and extracted from 40 invasive primary breast tumors, seven lymph node and skin metastases, nine metastatic effusions, and five established breast cancer cell lines. The polymerase chain reaction technique was used to amplify DNA fragments containing Kirsten-(Ki-), Harvey-(Ha-), and N-ras codons 12, 13, and 61 which were then probed on slot-blots with labeled synthetic oligomers to detect nonconservative single base mutations. Activating mutations were found in one of 40 primary tumors (Ki-ras codon 13), zero of seven lymph node and skin metastases, one of nine metastatic effusions (Ki-ras codon 12), and two of five cell lines (Ki-ras codons 12 and 13). These results indicate that activating ras mutations are rarely involved in either the initiation or metastatic progression of human breast cancer.
为了验证ras激活参与乳腺癌进展最后阶段这一假说,我们分析了来自60位不同患者的肿瘤DNA,这些DNA取自40例浸润性原发性乳腺癌、7例淋巴结及皮肤转移灶、9例转移性积液以及5种已建株的乳腺癌细胞系。采用聚合酶链反应技术扩增包含Kirsten-(Ki-)、Harvey-(Ha-)和N-ras密码子12、13及61的DNA片段,然后用标记的合成寡核苷酸在狭缝印迹上进行检测,以发现非保守性单碱基突变。在40例原发性肿瘤中有1例发现激活突变(Ki-ras密码子13),7例淋巴结及皮肤转移灶中未发现激活突变,9例转移性积液中有1例发现激活突变(Ki-ras密码子12),5种细胞系中有2例发现激活突变(Ki-ras密码子12和13)。这些结果表明,激活的ras突变很少参与人类乳腺癌的起始或转移过程。