NM23 GENE-EXPRESSION CORRELATES WITH CELL-GROWTH RATE AND S-PHASE

Two human NM23 genes have been identified: NM23.H1 and NM23.H2 coding for the A and B subunit of a nucleoside diphosphate kinase (NDPK), res pectively. NM23.H1 gene has been proposed as a suppressor of metastati c ability in tumor cells, NM23.H2 is identical to the c-myc transcript ion factor, pup. The NM23 coding sequence is strongly preserved throug h different species. Indirect evidence of various types has been accum ulated and seems to support an implication of NM23 in cell proliferati on. This report shows that the NM23 gene expression is strictly relate d to the growth state of the cells. Two different in vitro systems (hu man peripheral blood lymphocytes and human breast epithelial cell line MCF-10A) and one in vivo (human primary infiltrating ductal breast ca rcinomas) system have been investigated. The mRNA is present in PHA-st imulated peripheral blood lymphocytes, whereas it is nearly undetectab le in their resting counterparts. The level of the NM23 gene expressio n parallels the fraction of cells incorporating thymidine (S-phase) in neoplastic mammary tissues. In synchronously cycling MCF-10A cells NM 23.H1 mRNA reaches a maximum abundance in the S-phase and is absent or only present at very low levels during G(0)/G(1) phase, whereas NM23. H2 is present in growth-arrested cells but is upregulated following se rum growth stimulation. (C) 1995 Wiley-Liss, Inc.