title: Modulation of retinoic Acid receptor-alpha, growth-factors and protooncogenes in retinoic Acid-induced apoptosis of ki-1 lymphoma cell-line.
abstract: We have previously reported the successful salvage by retinoid acid (RA) of patients with refractory Ki-1 lymphoma. In this study, we have further investigated the effect of all-trans RA on a Ki-1 lymphoma cell line SR786. Similar to the clinical observation, SR786 cells were sensitive to RA treatment (ID50=0.6 mu m). RA-treated SR786 cells were transformed to a more differentiated morphology at 24 h, and subsequently died via apoptosis at 48-72 h. This process was associated with a decreased expression of the proliferation markers and c-myc proto-oncogene. The RA receptor alpha (RAR-alpha), however, showed an immediate enhanced expression at 1/2 h, and followed by an increase of transforming growth factor-beta 1 (TGF-beta 1) gene expression. The apoptosis and increased expression of TGF-beta 1 could be completely blocked;by the addition of cycloheximide given within 12 h of RA treatment. It appears that the RA-induced apoptosis of SR-786 is the result of an RA-induced upregulation of RAR-alpha and a subsequent activation of TGF-beta 1, which in turn leads to a cascade of the suppression of growth-related genes. Our observations strongly support the use of retinoids in Ki-1 lymphoma and invite further studies to test the potential of RA in other specific type T-cell lymphomas.
authors.affiliation: NATL TAIWAN UNIV,COLL MED,DEPT PATHOL,TAIPEI 10764,TAIWAN. NATL TAIWAN UNIV,COLL MED,DEPT INTERNAL MED,TAIPEI 10764,TAIWAN.
authors.forename: I
authors.initials: I
authors.lastname: Su
authors.forename: Z
authors.initials: Z
authors.lastname: Lay
authors.forename: A
authors.initials: A
authors.lastname: Cheng
authors.forename: Y
authors.initials: Y
authors.lastname: Chang