Differential effects of p19(Arf) and p16(Ink4a) loss on senescence of murine bone marrow-derived preB cells and macrophages.

ABSTRACT: Establishment of cell lines from primary mouse embryo fibroblasts depends on loss of either the Arf tumor suppressor or its downstream target, the p53 transcription factor. Mouse p19(Arf) is encoded by the Ink4a-Arf locus, which also specifies a second tumor suppressor protein, the cyclin D-dependent kinase inhibitor p16(Ink4a). We surveyed bone marrow-derived cells from wild-type, Ink4a-Arf-null, or Arf-null mice for their ability to bypass senescence during continuous passage in culture. Unlike preB cells from wild-type mice, those from mice lacking Arf alone could be propagated indefinitely when placed onto stromal feeder layers engineered to produce IL-7. The preB cell lines remained diploid and IL-7-dependent and continued to express elevated levels of p16(Ink4a). By contrast, Arf-nul

SUBMITTER: Randle DH 

PROVIDER: S-EPMC55507 | biostudies-literature | 2001 Aug

REPOSITORIES: biostudies-literature