DIFFERENTIAL SUPPRESSION OF MAMMARY-CANCER AND PROSTATE-CANCER METASTASIS BY HUMAN CHROMOSOME-17 AND CHROMOSOME-11

Metastasis suppressor activities have previously been mapped to human chromosomes 17 and 11. Decreased expression of the metastasis suppress or gene NM23, which is located on chromosome 17, has been correlated w ith increased metastatic potential in mammary cancers. A region on hum an chromosome 11, from 11p11.2p13, has been shown to suppress metastas is in rat prostatic carcinoma cells. in both cases the metastasis supp ressor activity had no effect on tumorigenicity or tumor growth rate, demonstrating that the encoded activities are distinct from effects of tumor suppression. To determine whether these human chromosomes encod e general or tissue-specific metastasis suppressor activities, a trunc ated human chromosome 17 (ie., pter-q23) and a full-length human chrom osome 11 were separately transferred into highly metastatic rat mammar y and prostate cancer cell lines and tested for their ability to suppr ess spontaneous metastasis in vivo. These studies demonstrated that wh en the pter-q23 region of human chromosome 17 is retained by the micro cell hybrids, the metastatic ability of both mammary and prostatic can cer cells is suppressed. In contrast, when the pter-q14 region of huma n chromosome 11 is retained, only the metastatic ability of prostatic cancer cells is suppressed. Additional studies demonstrated that the m etastasis suppressor activity encoded by the chromosome 17 pter-q23 re gion is p53-independent and not due to enhanced expression of NM23 pro tein.