Gamma-interferon induces an irreversible growth arrest in mid-G1 in mammary epithelial cells which correlates with a block in hyperphosphorylation of retinoblastoma

摘要: In this study, we analyze effects of IFN-gamma on the proliferation normal human mammary epithelial cells (MECs) and several carcinoma cell lines. We demonstrate that blocks MECs in a time- concentration-dependent manner. This growth arrest is irreversible occurs at specific stage G1 phase cycle. caused rapid (within 12-24 h) down-regulation cyclin A, c-myc, cdc2 proteins, as well disappearance hyperphosphorylated forms retinoblastoma family Rb p130. The synthesis other control p53, p21/Waf1, proliferating nuclear antigen, was down-regulated between 24 48 h. synchronized by epidermal factor deprivation released for cycle traverse re-addition to medium, able block DNA only if added first 6 7 h after factor. phosphorylation A expression coordinately regulated during same narrow window G1. Several lines demonstrated resistance growth-inhibitory did not exhibit or change hyperphosphorylation when treated with IFN-gamma. Initial studies suggest, some lines, may be defects signal transduction pathway (measured IFN-gamma-responsive gene GBP), while others due regulatory proteins are targets action.