Methylthioadenosine Phosphorylase, a Gene Frequently Codeleted with p16cdkN2a/ARF, Acts as a Tumor Suppressor in a Breast Cancer Cell Line

摘要: The human methylthioadenosine phosphorylase (MTAP) gene is located on 9p21 and frequently homozygously deleted, along with p16cdkN2a/ARF, in a wide variety of tumors tumor-derived cell lines. function MTAP to salvage methylthioadenosine, which produced as byproduct polyamine metabolism. We have reintroduced into MCF-7 breast adenocarcinoma cells examined its effect the tumorigenic properties these cells. expression does not affect growth rate standard tissue culture conditions but severely inhibits their ability form colonies soft agar or collagen. In addition, MTAP-expressing are suppressed for tumor formation when implanted SCID mice. This suppression anchorage-independent appears be because enzymatic activity MTAP, protein missense mutation active site exhibit this phenotype. causes significant decrease intracellular levels alters ratio putrescine total polyamines. Consistent observation, biosynthesis inhibitor α-difluoromethylornithine MTAP-deficient agar, whereas addition stimulates colony These results indicate that has suppressor suggest effects may mediated by altering pools.