INCREASED NM23-H1 AND NM23-H2 MESSENGER-RNA EXPRESSION AND ABSENCE OF MUTATIONS IN COLON CARCINOMAS OF LOW AND HIGH METASTATIC POTENTIAL

被引:76
作者
MYEROFF, LL
MARKOWITZ, SD
机构
[1] CASE WESTERN RESERVE UNIV,DEPT MED,CLEVELAND,OH 44106
[2] UNIV HOSP CLEVELAND,IRELAND CANC CTR,CLEVELAND,OH 44106
关键词
D O I
10.1093/jnci/85.2.147
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:147 / 152
页数:6
相关论文
共 22 条
[1]  
BEVILACQUA G, 1989, CANCER RES, V49, P5185
[2]   ASSOCIATION OF NM23-H1 ALLELIC DELETIONS WITH DISTANT METASTASES IN COLORECTAL-CARCINOMA [J].
COHN, KH ;
WANG, FS ;
DESOTOLAPAIX, F ;
SOLOMON, WB ;
PATTERSON, LG ;
ARNOLD, MR ;
WEIMAR, J ;
FELDMAN, JG ;
LEVY, AT ;
LEONE, A ;
STEEG, PS .
LANCET, 1991, 338 (8769) :722-724
[3]  
DAVIS LG, 1986, BASIC METHODS MOL BI, P130
[4]  
GILLES AM, 1991, J BIOL CHEM, V266, P8784
[5]   INDUCTION OF NM23 GENE-EXPRESSION IN HUMAN COLONIC NEOPLASMS AND EQUAL EXPRESSION IN COLON TUMORS OF HIGH AND LOW METASTATIC POTENTIAL [J].
HAUT, M ;
STEEG, PS ;
WILLSON, JKV ;
MARKOWITZ, SD .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1991, 83 (10) :712-716
[6]   EXPRESSION OF THE ANTIMETASTATIC GENE NM23 IN HUMAN BREAST-CANCER - AN ASSOCIATION WITH GOOD PROGNOSIS [J].
HENNESSY, C ;
HENRY, JA ;
MAY, FEB ;
WESTLEY, BR ;
ANGUS, B ;
LENNARD, TWJ .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1991, 83 (04) :281-285
[7]   POSITIVE RELATIONSHIP BETWEEN EXPRESSION OF ANTIMETASTATIC FACTOR (NM23-GENE PRODUCT OR NUCLEOSIDE DIPHOSPHATE KINASE) AND GOOD PROGNOSIS IN HUMAN BREAST-CANCER [J].
HIRAYAMA, R ;
SAWAI, S ;
TAKAGI, Y ;
MISHIMA, Y ;
KIMURA, N ;
SHIMADA, N ;
ESAKI, Y ;
KURASHIMA, C ;
UTSUYAMA, M ;
HIROKAWA, K .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1991, 83 (17) :1249-1250
[8]   ALLELIC LOSS IN COLORECTAL-CARCINOMA [J].
KERN, SE ;
FEARON, ER ;
TERSMETTE, KWF ;
ENTERLINE, JP ;
LEPPERT, M ;
NAKAMURA, Y ;
WHITE, R ;
VOGELSTEIN, B ;
HAMILTON, SR .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1989, 261 (21) :3099-3103
[9]   REDUCED TUMOR-INCIDENCE, METASTATIC POTENTIAL, AND CYTOKINE RESPONSIVENESS OF NM23-TRANSFECTED MELANOMA-CELLS [J].
LEONE, A ;
FLATOW, U ;
KING, CR ;
SANDEEN, MA ;
MARGULIES, IMK ;
LIOTTA, LA ;
STEEG, PS .
CELL, 1991, 65 (01) :25-35
[10]  
LEONE A, 1991, CANCER RES, V51, P2490