Consistent inactivation of @entity7000 but not XXXX ( @entity3722 ) in @entity19 myeloid cells transformed in vivo by deregulated c-Myc.

@entity1 @entity851 @entity7000 @entity899 @entity5 @entity19 @entity3052 @entity1778 @entity1583 @entity1167 @entity3842 @entity3722
Cyclin-dependent kinase inhibitors @entity3842 ( @entity3842 ) and @entity3722 ( @entity3722 ), encoded by the @entity3842 loci, play an important role in negative regulation of the cell cycle. Furthermore, @entity7000 (ARF) also encoded by the @entity3842 locus, has been shown to regulate positively the @entity899 pathway leading to growth arrest and apoptosis. All three genes have been inactivated in @entity1 @entity5 . In myeloid cells, @entity3722 ( @entity3722 ) mRNA is upregulated during cytokine-induced @entity851 , and hypermethylation of the @entity3722 ( @entity3722 ) gene promoter region is a common event in @entity3052 . In the present study, we examined @entity19 monocyte/macrophage @entity5 with deregulated c-myc for evidence of Ink4 gene inactivation. @entity3722 ( @entity3722 ) mRNA and protein were detected in the majority of @entity1778 , and @entity3842 ( @entity3842 ) mRNA and protein were highly expressed in two of them. pRb was in a hypophosphorylated state in most of the @entity5 indicating that the Cdk inhibitors that were expressed in the cells were functional. The observed expression of @entity3722 ( @entity3722 ) is inconsistent with their proliferation state, although it might be expected to be expressed owing to the maturity of the cells. These data suggest, therefore, that deregulated c-Myc bypasses the pRb restriction point and cell cycle arrest in these @entity5 . An examination of @entity7000 (Arf) exons revealed deletions of the gene in up to 94% of the @entity5 . Since this gene shares exon 2 with @entity3842 ( @entity3842 ), it is often difficult to determine which gene is the relevant @entity5 suppressor. However, the loss of only the @entity7000 was observed in a @entity5 that had normal @entity3842 ( @entity3842 ) protein expression. In addition, the @entity7000 (Arf)-specific exon was deleted in another @entity5 that expressed a functional chimeric protein, p15Ex1-p16Ex2-3; it was demonstrated here that this fusion protein is capable of inducing @entity1167 . These data overall supports the hypothesis that the critical inactivation event in these @entity1583 is elimination of @entity7000 (Arf), and not Ink4 function.
