Abstract
The metastasis-suppressor nme gene (also called nm23), first identified in murine melanoma cells, exists as two forms in human: nme1 and nme2. However, only the lack of expression of nme1 has been related to distant metastasis appearance in human breast cancer. The aim of this work was first to raise specific antibodies to allow the analysis of Nme1 and then, with this specific tool, to evaluate the predictive value of Nme1 detection in cytosolic extracts of human breast tumours. We obtained a hen antibody that specifically reacts with Nme1 without any cross-reaction with Nme2. We analysed the expression of the protein in 59 human breast tumours and found a significant relationship between this expression and oestrogen receptor status (P<0.001). Moreover, Nme1 expression is related to metastasis-free survival (P<0.001) and survival of patients (P<0.001). The determination of Nme1 expression in primary tumours using our antibody should be an interesting predictive test of the metastasis for clinical investigations.
Highlights
The metastasis-suppressor gene, nmel was identified in 1988 (Steeg et al, 1988) by differential hybridisation between low and high metastatic murine melanoma cell lines: the mRNA expression of this gene was found to be higher in the low metastatic cell line
Only the lack of expression of nmel has been related to distant metastasis appearance in human breast cancer
The aim of this work was first to raise specific antibodies to allow the analysis of Nmel and with this specific tool, to evaluate the predictive value of Nmel detection in cytosolic extracts of human breast tumours
Summary
The metastasis-suppressor gene, nmel was identified in 1988 (Steeg et al, 1988) by differential hybridisation between low and high metastatic murine melanoma cell lines: the mRNA expression of this gene was found to be higher in the low metastatic cell line. The nme gene family consists of two closely related genes: nmel and nme, which respectively code for two different subunits (A and B) of nucleotide diphosphate kinases (NDP kinases) (Gilles et al, 1991). These two subunits, which show more than 88% homology, associate together in different ratios according to tissue location, to form hexameric NDP kinases. This class of enzymes is involved in microtubule association (Nickerson and Wells, 1991) and G-protein regulation (Kimura and Shimada, 1988) but the precise molecular mechanism underlying the role of nme genes in metastasis dissemination is still unclear. Postel et al (1993) has suggested that the Nme protein is a transcription factor for the c-myc oncogene
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