title: Hematopoietic malignancies associated with increased Stat5 and Bcl-x(L) expressions in Ink4a/Arf-deficient mice.
abstract: 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 Ink4a/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.
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Sung
authors.forename: Junghwan
authors.initials: J
authors.lastname: Park
authors.forename: Bongkun
authors.initials: B
authors.lastname: Choi
authors.forename: Jaehong
authors.initials: J
authors.lastname: Kim
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Choi
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Yang
authors.forename: Minjae
authors.initials: M
authors.lastname: Lee
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Han
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Han
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Kim
authors.forename: Jaewhan
authors.initials: J
authors.lastname: Song
authors.forename: Kunsoo
authors.initials: K
authors.lastname: Rhee
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism*; D006410:Hematopoiesis; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis*; D025803:Tumor Suppressor Protein p14ARF / Q000172:deficiency*; D051020:bcl-X Protein
chemical_list: C494812:Bcl2l1 protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D025803:Tumor Suppressor Protein p14ARF; D051020:bcl-X Protein