title: RU486 inhibits glucocorticoid hormone-dependent oncogenesis by human papillomavirus type 16 DNA.
abstract: We have previously reported (Pater et al., Nature 335, 832-835, 1988) the glucocorticoid hormone-dependent oncogenic transformation of primary baby rat kidney (BRK) cells by a combination of human papillomavirus (HPV) type 16 DNA and the activated form of the human Ha-ras-1 (ras) oncogene. In this study we provide evidence for the inhibition of such hormone-dependent transformation by the hormone antagonist, RU486. The level of inhibition was dependent on the ratio of hormone to antagonist and severe inhibition was observed at a 1:5 ratio. The effect of RU486 on the growth of HPV16-transformed cells was also studied. Severe growth inhibition and cell death occurred when cells transformed in the absence of RU486 were subsequently grown in the presence of either a 1:2.5 or 1:5 ratio of hormone to hormone antagonist. RU486 did not alter the level or electrophoretic mobility pattern of HPV16 mRNA expressed in transformed cells, when antihormone was applied either continuously or subsequent to transformation by HPV. These results indicate the importance of continuous viral gene expression for initiation and maintenance of the transformed phenotype.
authors.affiliation: Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: M M
authors.initials: MM
authors.lastname: Pater
authors.forename: A
authors.initials: A
authors.lastname: Pater
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002472:Cell Transformation, Viral / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology*; D027383:Papillomaviridae / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D015735:Mifepristone