ACTIVATED PRODUCTION OF METALLOPROTEINASES IN KI-RAS-TRANSFORMED HUMAN OSTEOSARCOMA CELLS

The human osteosarcoma cell culture HOS does not produce matrix metall oproteinases (MPs)(1). However, after transformation with the Ki-ras o ncogene, the resulting culture (KHOS) produced readily detectable MPs. The molecular weight of the major MP was 66 kDa, while the molecular weights of two other minor bands were 71 kDa and 60 kDa. The activity of all three enzymes was inactivated by treatment with ethylene diamin etetra acetic acid, indicating that they are probably MPs. The substra te preference of the 66-kDa MP (in decreasing order) was gelatin and c ollagens V, I, III, and IV. Treatment of the MPs with p-aminophenylmer curic acetate led to the appearance of 62- kDa activated enzyme. The M P produced by KHOS cells did not react with the monoclonal anti-rat st romelysin antibody MC. Treatment of KHOS cells with retinoic acid and dexamethasone, which are known to suppress c-fos/c-jun and AP-1, suppr essed the production of the MPs. Therefore, the activation of MPs by K i-ras in KHOS cells may involve c-fos/c-jun and the AP-1-responsive pa thway.