title: Transformation reversion induced in JB6 RT101 cells by AP-1 inhibitors.
abstract: The present study was directed to characterizing the reversion of neoplastic epidermal JB6 RT101 cells by AP-1 inhibiting drugs. Treatment of tumorigenic JB6 RT101 cells with retinoic acid (RA), fluocinolone acetonide (FA) or forskolin (FN) induced drug dependent (reversible) reversion of transformation. A synergistic effect on reversion was found with the three drugs in combination. Cells reverted by these three drugs also showed reduced levels of AP-1 transcription factor activity. After long term exposure of RT101 cells to FA, enrichment of flat revertants occurred in the population while a few unreverted cells formed foci. These unreverted cells appeared to be FA-resistant. Cloning of cells following RA treatment revealed stable reversion at least 2 months after drug withdrawal. Stable revertants showed lower basal AP-1 activity than RT101 cells (P < 0.01) and unstable revertants returned to transformed phenotype and elevated AP-1 activity within days following drug withdrawal. To our knowledge this is the first demonstration that drug induced reversion co-selects for reduced AP-1 activity. These data suggest that the JB6 RT101 cell line is a useful cell model for studying reversion of transformation and that inhibition of AP-1 activity may be one molecular mechanism of reversion. Considering the development of resistance with FA alone and the relative inefficiency of RA or FN alone, combinations of the three AP-1 activity inhibitors RA, FA and FN may be useful for further animal and clinical studies.
authors.affiliation: Biological Carcinogenesis & Development Program, PRI/DynCorp, Frederick, MD, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: V
authors.initials: V
authors.lastname: Lavrovsky
authors.forename: N H
authors.initials: NH
authors.lastname: Colburn
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D005576:Colforsin / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000378:metabolism; D004351:Drug Resistance; D005446:Fluocinolone Acetonide / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000235:genetics; D051379:Mice; D010641:Phenotype; D012680:Sensitivity and Specificity; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D005938:Glucocorticoids; D018808:Transcription Factor AP-1; D005446:Fluocinolone Acetonide; D005576:Colforsin; D014212:Tretinoin; D000242:Cyclic AMP