INCREASED NM23-H1 AND NM23-H2 MESSENGER-RNA EXPRESSION AND ABSENCE OF MUTATIONS IN COLON CARCINOMAS OF LOW AND HIGH METASTATIC POTENTIAL
INCREASED NM23-H1 AND NM23-H2 MESSENGER-RNA EXPRESSION AND ABSENCE OF MUTATIONS IN COLON CARCINOMAS OF LOW AND HIGH METASTATIC POTENTIAL
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DOI：
10.1093/jnci/85.2.147
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发表时间：
1993-01-20
期刊：
影响因子：
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通讯作者：
MARKOWITZ, SD
中科院分区：
文献类型：
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作者：
MYEROFF, LL;MARKOWITZ, SD
背景资料：小鼠nm 23基因抑制恶性啮齿类肿瘤系的转移行为，并且nm 23表达降低与人乳腺癌淋巴结转移的可能性增加相关。最近的数据已经证明存在两种人类nm 23基因同源物，nm 23-H1和nm 23-H2，并且已经显示nm 23-H1等位基因的缺失发生在与不良预后相关的一些结肠癌中。这些结果表明，nm 23-H1编码抑制结肠癌转移。与此相反，我们以前曾报道，总nm 23信使RNA（mRNA）的表达增加到类似的水平，在结肠肿瘤的高和低转移潜力。目的：本研究旨在使我们以前的研究结果与最近报道的nm 23-H1等位基因缺失与人类结肠癌预后不良相关。我们的目的是研究人类结肠癌的失活的两个候选转移抑制基因，nm 23-H1和nm 23-H2，无论是突变或基因转录的损失。研究方法：我们使用核糖核酸酶保护试验来分析人结肠肿瘤的nm 23-H1（43个样品）和nm 23-H2（41个样品）转录物（mRNA）表达水平以及可能破坏潜在抑制功能的突变的存在。结果：仅检测到野生型nm 23-H1和nm 23-H2 mRNA。41例结肠肿瘤中33例nm 23-H1 mRNA表达较正常结肠组织增高，28例nm 23-H2 mRNA表达较正常结肠组织增高。这些mRNA水平的增加在低转移潜能和高转移潜能的肿瘤中是相似的。结论：这些结果表明，尽管nm 23-H1等位基因缺失与结肠癌预后不良相关，但nm 23-H1和nm 23-H2等位基因并不直接介导结肠癌的转移抑制。我们的研究结果没有解释nm 23-H1等位基因缺失与结肠癌转移潜能相关的观察结果。含义：这些发现也与nm 23在小鼠黑色素瘤中的转移抑制活性的证明以及nm 23表达缺失与乳腺癌预后不良的相关性形成对比。nm 23基因的转移抑制可能是一种组织特异性现象。
Background: The murine nm23 gene suppresses the metastatic behavior of malignant rodent tumor lines, and reduced nm23 expression correlates with increased likelihood of lymph node metastases in human breast cancers. More recent data have demonstrated the existence of two human nm23 gene homologues, nm23-H1 and nm23-H2, and have shown that deletion of nm23-H1 alleles occurs in some colon carcinomas associated with poor prognosis. These findings suggest that nm23-H1 encodes for suppression of colon carcinoma metastasis. In contrast, we have previously reported that total nm23 messenger RNA (mRNA) expression is increased to similar levels in colon tumors of both high and low metastatic potential. Purpose: This study was designed to reconcile our previous findings with the recent report of nm23-H1 allelic deletion in human colon cancers associated with poor prognosis. Our purpose was to examine human colon cancers for inactivation of two candidate metastasis suppressor genes, nm23-H1 and nm23-H2, either by mutation or by loss of gene transcription. Methods: We used ribonuclease protection assays to analyze human colon tumors for the level of nm23-H1 (43 samples) and nm23-H2 (41 samples) transcript (mRNA) expression and the presence of mutations that could inactivate potential suppressor function. Results: We detected only wild-type nm23-H1 and nm23-H2 mRNA. Expression of nm23-H1 mRNA increased in 33 of 41 colon tumors, and expression of nm23-H2 mRNA was elevated in 28 of 41 colon tumors relative to that in matched normal mucosa. Increases in these mRNA levels were similar in tumors of both low and high metastatic potential. Conclusions: These results suggest that, despite correlation of nm23-H1 allelic deletions with colon cancers associated with poor prognosis, nm23-HI and nm23-H2 alleles do not directly mediate metastasis suppression in colon carcinoma. Our results leave unexplained the observation that nm23-H1 allelic deletion correlates with metastatic potential of colon carcinomas. Implications: These findings also contrast with the demonstration of nm23 metastasis suppressor activity in murine melanoma and with the correlation of loss of nm23 expression in breast cancer with poor prognosis. It may be that metastasis suppression by the nm23 gene is a tissue-specific phenomenon.