INDUCTION OF NM23 GENE-EXPRESSION IN HUMAN COLONIC NEOPLASMS AND EQUAL EXPRESSION IN COLON TUMORS OF HIGH AND LOW METASTATIC POTENTIAL

INDUCTION OF NM23 GENE-EXPRESSION IN HUMAN COLONIC NEOPLASMS AND EQUAL EXPRESSION IN COLON TUMORS OF HIGH AND LOW METASTATIC POTENTIAL
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DOI:
10.1093/jnci/83.10.712
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发表时间:
1991-05-15
期刊:
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子:
--
通讯作者:
MARKOWITZ, SD
MARKOWITZ, SD
中科院分区:
其他
文献类型:
--
作者:
HAUT, M;STEEG, PS;MARKOWITZ, SD

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在几种啮齿动物肿瘤模型系统中,小鼠nm 23基因的表达水平与转移潜能呈负相关。 人nm 23同源物在高转移潜能的人乳腺癌中的表达也低于在高转移潜能的乳腺癌中的表达,低于在低转移潜能的乳腺癌中的表达。 在本研究中,我们研究了nm 23表达的变化,在结肠癌发生过程中发现在18对匹配的正常和肿瘤的人结肠组织。 我们发现,在形态正常的结肠粘膜的所有样品中表达0.8-丝氨酸蛋白酶nm 23转录。 在18例结肠肿瘤中的16例中,nm 23表达在肿瘤中进一步增加,与形态正常的结肠粘膜相比,来自同一个体。 nm 23的表达高于正常粘膜3息肉,在2 3非转移性癌症,并在11 12个癌症转移在最初的介绍。 nm 23在12例转移性结肠癌和6例临床分期较低的结肠癌中的表达水平相似。 此外,nm 23表达维持在12个细胞系中的每一个从人结肠肿瘤的培养,并没有不同的线之间建立的肿瘤的高或低转移能力。 结论nm 23在正常结肠粘膜中有表达。 nm 23的表达在结肠癌发生的早期阶段增加,并在转移性结肠癌中保持增加。 因此,在结肠中,组织特异性事件使nm 23表达与肿瘤转移能力丧失分离。
Levels of expression of the murine nm23 gene inversely correlate with metastatic potential in several rodent tumor model systems. Expression of the human nm23 homologue also is lower in human breast cancers of high metastatic potential than in breast cancers of high metastatic potential than in breast cancer of low metastatic potential. In the present study, we examined changes in nm23 expression during colon carcinogenesis as found in 18 matched pairs of normal and neoplastic human colon tissues. We found that a 0.8-kilobase nm23 transcript was expressed in all samples of morphologically normal colon mucosa. In 16 of 18 colon neoplasms, nm23 expression was further increased in the neoplastic, compared with the morphologically normal, colon mucosa from the same individual. Expression of nm23 was elevated over normal mucosa in 3 of 3 polyps, in 2 of 3 nonmetastatic cancers, and in 11 of the 12 cancers that were metastatic at the initial presentations. The levels of nm23 expressed were similar in the 12 metastatic colon neoplasms and in the 6 colon neoplasms of lower clinical stage. In addition, nm23 expression was maintained in culture in each of 12 cell lines initiated from human colon neoplasms and did not differ between lines established from neoplasms of high or low metastatic capability. We concluded that nm23 was expressed in normal colon mucosa. Expression of nm23 increased during early stages of colon carcinogenesis and remained increased in metastatic colon cancer. Therefore, in the colon, tissue-specific events dissociated nm23 expression from loss of tumor metastatic competence.