Hematopoietic malignancies associated with increased Staff and Bcl-xL expressions in Ink4a/Arf-deficient mice

초록

The INK4a/ARF locus, which encodes the two distinct proteins p16(INK4a) and p14(ARF) is frequently altered in various hematological malignancies as well as in other types of cancers in humans. In this study, we surveyed tumors that had spontaneously developed in InNa/Arf-deficient mice with an inbred FVB/NJ genetic background. We found that an Ink4a/Arf-deficiency exerted more severe effects on the induction of hematopoietic malignancies in mice with an inbred FVB/NJ genetic background than in mice with a mixed genetic background. We also provided the evidence that this prevalence of hematopoietic malignancies in Ink4a/Arf-deficient mice is associated with the upregulated expressions of Stat5 and its transcriptional target, Bcl-x(L), both of which are involved in the regulation of hematopoiesis. These results suggest a possible implication of the Ink4a/Arf locus in the control of hematopoietic pathways by negatively regulating the Stat5-signalling pathways. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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