MAPPING OF METASTASIS SUPPRESSOR GENE(S) FOR RAT PROSTATE-CANCER ON THE SHORT ARM OF HUMAN-CHROMOSOME-8 BY IRRADIATED MICROCELL-MEDIATED CHROMOSOME TRANSFER

Our previous studies demonstrated that human chromosome 8 contains met astasis suppressor gene(s) for rat prostate cancer, However, it is sti ll unknown which portion of human chromosome 8 is associated with supp ression of metastatic ability, because all of the clones in which meta static ability is suppressed contain at least one copy of intact human chromosome 8, In the present study, we used the irradiated microcell- mediated chromosome transfer technique to enrich for specific chromoso mal arm deletions of selected chromosomes. The resultant series of hum an chromosomes 8 with a variety of chromosomal deletions was introduce d into highly metastatic Dunning rat prostate cancer cells, All of the resultant microcell hybrids showed reduced metastatic ability. To obt ain a smaller size of human chromosome 8 and to locate further the reg ion of metastasis suppressor gene(s), the most reduced size of human c hromosome 8 that was generated with the initial irradiated chromosome transfer was retransferred into the Dunning cancer cells without irrad iation. The resultant microcell hybrids were analyzed to determine whi ch portion of human chromosome 8 suppressed the metastatic ability of the recipient cells, This analysis demonstrates that the portion of hu man chromosome 8 containing metastasis suppressor gene(s) for rat pros tate cancer cells lies on human chromosome segment 8p21-p12, where fre quent allelic losses have been detected in allelotype analyses of huma n prostate cancer. This suggests that one of the metastasis suppressor genes for rat prostate cancer on human chromosome 8 may also play an important role in the progression of human prostate cancer. (C) 1996 W iley-Liss, Inc.