EFFECTS OF BRYOSTATINS AND RETINOIC ACID ON PHORBOL ESTER-INDUCED AND DIACYLGLYCEROL-INDUCED SQUAMOUS DIFFERENTIATION IN HUMAN TRACHEO-BRONCHIAL EPITHELIAL-CELLS

  • 15 July 1989
    • journal article
    • research article
    • Vol. 49  (14) , 3990-3995
Abstract
Previous studies have shown that normal human tracheobronchial epithelial (HBE) cells undergo squamous differentiation upon treatment with phorbol-12-myristate-13-acetate (PMA). In this study, we report that induction of this differentiation program is accompanied by an increase in the accumulation of cholesterol sulfate and in transglutaminase type I activity, two markers of squamous differentiation. Several carcinoma cell lines did not exhibit an increase in these differentiation markers after PMA-treatment and appear to have acquired a defect in the mechanism that triggers differentiation. The diacyglycerol analogue, didecanoylglycerol (diC10), was also able to induce squamous differentiation. Brostatin 1, another activator of protein kinase C, did not induce terminal cell division or increase cholesterol sulfate accumulation or transglutaminase type I activity. Bryostatin 1 not only failed to inhibit cell proliferation and to induce differentiation but antagonized the PMA-and diC10-induced commitment to terminal differentiation. The bryostain blocked both the PMA-induced terminal cell division as well as the expression of the two differentiation markers. Retinoids were found not to affect the PMA-induced commitment to terminal cell division but did inhibit the expression of the differentiated phenotype. Our results indicate that the byrostatins and retinoids affect the multistep process of squamous differentiation in tracheobronchial epithelial cells at two different stages.