Short term (median follow-up of 16 months) clinical course data were consistent with nm23 RNA levels, in that 2 of 11 low nm23 RNA content patients (including one from the 0 involved lymph node group) developed metastases, while none of the high nm23 RNA patients have experienced recurrent disease.
The product of the abnormal wing discs (awd) gene of Drosophila is 78% identical to the product of the nm23 gene of mammals, which is differentially expressed in certain metastatic tumors.
Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value.
Our findings indicate that, in contrast to a proposed role for nm23-H1 as a tumor metastasis suppressor, increased p19/nm23 protein in neuroblastoma is correlated with features of the disease that are associated with aggressive tumors.
It was found that patients developing metastases during the first 2 years after diagnosis had significantly lower levels of tumor nm23 expression (56% of the mean value) compared to patients with less aggressive disease (164%) (P < 0.0004).
These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.
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.
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.
In addition, we correlated the findings with other relevant molecular markers including the metastasis associated nm23-H1 gene and loss of heterozygosity (LOH) using multiple polymorphic markers for chromosome 17p and sequencing the entire open reading frame (ORF) of the p53 gene.
These results provide first evidence for novel mutation in the nm23 gene and demonstrate a correlation between the mutation in the nm23 gene and metastasis in colorectal oncogenesis which suggests that the nm23 gene plays a role in the causation of metastasis.
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.
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.
The time from biopsy of the primary MM to the appearance of the first lymph node metastasis also showed a positive correlation with the nm23 mRNA level in this metastasis.