A NOVEL MODEL FOR METASTASIS SUPPRESSION INVOLVING REGULATION OF NUCLEAR PRECURSOR MESSENGER-RNA STABILITY

Our previous data correlated urokinase plasminogen activator (uPA) gen e activation with metastasis in different rat mammary carcinomas, Howe ver, inconsistent with this was the suppression of the uPA gene in the metastatic rat mammary carcinoma cell line, BC1. We have now re-exami ned this cell line, selecting in vivo specifically for those BC1 cells capable of lung metastasis. We demonstrate that within the polyclonal BC1 cell line, it is possible to enrich for a metastatic sub-populati on which synthesizes 4 to 5-fold higher levels of uPA mRNA and enzyme activity. Therefore, the ability of a BC1 cell to metastasize appears to correlate with its escape from suppression of the uPA gene in this tumour. The results are consistent with the mechanism of uPA gene acti vation in metastatic DMBA-8 rat mammary tumour cells, and suggest a no vel model of tumour progression based on regulation of pre-mRNA stabil ity.