Kinetic Analysis of Hydrocortisone Effect on the Neodifferentiation of Kirsten Murine Sarcoma Virus-Transformed Human Skin Fibroblasts to Adipose Cells

Abstract

Here we have demonstrated that transformation of human skin fibroblasts (SF) by the Kirsten murine sarcoma virus (KiMSV) is Associated with their neodifferentiation into preadipose cells. Hydrocortisone (HC) and dexamethasone (DX) promoted the transformation/neodifferentiation of preadipocytes into mature fat cells. The effects of HC on the expression of adipocyte-containing foci (ACF) and on the total number of transformed foci (TTF) present in KiMSV-treated SF cultures were optimal at a concentration of about 500 ng/ml, or 1.25 × 10⁻-⁶ M. At this concentration of HC, the occurrence of ACF varied between 25 and up to 100% of the TTF formed in virus-treated cell cultures. In contrast, equimolar concentrations of estrogenic, androgenic, or progestational steroids inhibited ACF formation. The continued presence of HC post virus inoculation was necessary to effect optimal adipocytic conversion in KiMSV-treated cultures. Moreover, cell cultures that were “primed” with HC for up to 25 days or more prior to virus inoculation showed a further increase of ITF and of ACF at 14–21 days postinoculation. It is likely that the rasoncogene and HC can effect transformation/neodifferentiation of cells in a variety of normal or diseased human tissues de novo.