Genetic factors and metastatic potential of prostatic cancer

When a non-metastatic subline from the Dunning rat prostatic cancer was transfected with the v-Ha-ras oncogene, some transfectants acquired metastatic potential. Molecular analysis demonstrated that there was no simple dose-response relationship between v-Ha-ras expression and metastatic potential in this prostatic cancer system. Cytogenetic analysis on the same system demonstrated increased genetic instability following v-Ha-ras transfection. Progression of prostatic cancer from no metastatic to high metastatic potential may involve the loss of a metastasis suppressor gene. To test this possibility, non-metastatic and highly metastatic Dunning rat prostatic cancer cells were fused. Hybrid clones were isolated that conserved the chromosomes from their parental cells. When these hybrids were injected into animals, none developed distant metastases. When the non-metastatic primary tumours were passaged in vivo, distant metastases developed in occasional animals. Cytogenetic analysis of eight of these metastatic revertants demonstrated a consistent loss of normal chromosome 2. These studies show that metastasis is associated with the loss of a specific chromosome. These studies also suggest that a metastasis suppressor gene for rat prostatic cancer is located on chromosome 2. A more direct approach to identify a chromosome(s) carrying metastasis suppressor gene(s) by using microcell mediated chromosome transfer is currently progressing.