Hematopoietic malignancies associated with increased Stat5 and Bcl-x(L) expressions in Ink4a/Arf-deficient mice.
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.
Sung
Young Hoon
YH
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
Park
Junghwan
J
Choi
Bongkun
B
Kim
Jaehong
J
Cheong
Cheolho
C
Choi
Yoon Sik
YS
Yang
Eun Young
EY
Lee
Minjae
M
Han
Jin Soo
JS
Park
Sang Chul
SC
Han
Tae-Hee
TH
Kim
Tae Jin
TJ
Song
Jaewhan
J
Rhee
Kunsoo
K
Lee
Han-Woong
HW
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
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