Our purpose was to use this assay to investigate the role of the putative metastasis suppressor gene nm23-H1 in mammary development and differentiation.
In addition, there is evidence suggesting a contribution for the p53 and NF1 tumor-suppressor genes, and the nm23metastasis-suppressor gene, in melanoma development or progression.
A detailed study of the structure and function of the promoter element of the nm23-H1 gene will help in understanding the regulatory mechanisms of nm23 expression and its role in tumor progression, especially in metastasis.
These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.
In sharp contrast, the low frequency of loss at NME1 and its equal distribution in nodal metastasis-positive and -negative patients suggests that inactivation of this gene by allelic loss probably does not play a role in the development of regional metastases from these tumors.
Nm23 is a putative metastasis suppressor gene and alterations in this gene have been reported in colorectal carcinomas suggestive of a role for nm23 in the dissemination of these tumours.
We describe a serine phosphorylation of the putative metastasis suppressor protein Nm23, and present evidence of its relevance to the signal transduction and tumor metastatic processes.
It was suggested that the down-regulation of nm23 gene might have a role in metastasis and invasion in gastric cancer, possibly leading to a poor prognosis.
In Northern blot analysis an inverse relationship between metastatic ability and metastasis-suppressor gene, nm23-H1, expression is observed - with clone neo6/C8161.1 expressing the highest level of nm23 transcripts, neo6/C8161.2 and neo6/C8161.3 expressing intermediate levels, and barely detectable levels are seen in C8161.
To determine whether the nm23 genes could have a metastasis-suppressor function in non-small-cell lung carcinoma (NSCLC), pulmonary sarcoma and carcinoids, we analysed both nm23-HI and nm23-H2 mRNA levels in 37 tumor samples obtained from patients who underwent potentially curative resection between 1986 and 1990, and in 4 metastatic tumors obtained from autopsy.
Upon mammary fat pad or subcutaneous injection into nude mice, both the nm23-H1 and control transfected lines produced primary tumors; however, the nm23-H1-transfected lines produced metastases in significantly fewer mice than did control transfected lines.