Constitutive gene expression of four components of plasminogen activating enzyme system, urinary and tissue-type plasminogen activator (u-PA and t-PA), plasminogen activator inhibitor 1 (PAI-1) and PAI-2 in HT-1080 human fibrosarcoma cells, was modulated by the synthetic glucocorticoid dexamethasone (Dex, 10(-7) M).
A moderate heat stress, sufficient to induce heat shock protein 70 mRNA approximately 100-fold, resulted in a two- to three-fold increase in functionally active PAI-1 in the conditioned medium of human HT-1080 fibrosarcoma and Hep G2 hepatoma cells.
To determine whether the PKC and PKA pathways functionally interact during modulation of PAI gene expression, we assessed changes in gene transcription rates, mRNA, and antigen levels of PAI-1 and PAI-2 in HT-1080 fibrosarcoma cells treated with the PKC activator phorbol 12-myristate 13-acetate (PMA), alone or in combination with cAMP agonists and analogs.
A clone (1-3C), which shows low constitutive expression of PAI-1 and low metastatic potential to the lung, was selected from human fibrosarcoma cell line HT-1080.