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Elevated S-phase kinase-associated protein 2 protein expression in acute myelogenous leukemia: its association with constitutive phosphorylation of phosphatase and tensin homologue protein and poor prognosis

 Yoo Hong Min  ;  June-Won Cheong  ;  Yun Woong Ko  ;  Jee Sook Hahn  ;  Seung Tae Lee  ;  Ji Yeon Kim  ;  Mark Hong Lee 
 Clinical Cancer Research, Vol.10(15) : 5123-5130, 2004 
Journal Title
 Clinical Cancer Research 
Issue Date
Adolescent ; Adult ; Aged ; Blotting, Western ; Cell Cycle ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; Cytogenetics ; Cytoplasm/metabolism ; Female ; G1 Phase ; Humans ; Leukemia, Myeloid, Acute/metabolism* ; Male ; Middle Aged ; Multivariate Analysis ; Phosphoric Monoester Hydrolases/metabolism* ; Phosphorylation ; Prognosis ; S Phase ; S-Phase Kinase-Associated Proteins/biosynthesis* ; Signal Transduction ; Time Factors ; Treatment Outcome ; Tumor Suppressor Proteins/metabolism
PURPOSE: The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G(1)-S phase transition by controlling the stability of several G(1) regulators, such as p27Kip1. However, the clinical significance of Skp2 in patients with acute myelogenous leukemia (AML) remains unknown. EXPERIMENTAL DESIGN: We examined the clinical and biological significance of Skp2 expression in AML and evaluated the relationship between Skp2 and p27Kip1 expression and phosphatase and tensin homologue (PTEN) phosphorylation. RESULTS: Western blot analysis showed that high Skp2 expression was observed in 57 (57.6%) cases and significantly correlated with unfavorable cytogenetics (P = 0.035) but not with age, white blood cell count, serum lactic dehydrogenase level, and the French-American-British subtype. An inverse correlation was not observed between Skp2 and p27Kip1 expression. However, p27Kip1 protein was preferentially localized to cytoplasm in the high-Skp2-expression group. The cytoplasmic to nuclear ratio of p27Kip1 expression was significantly correlated with the levels of Skp2 expression (P < 0.001). The frequency of PTEN phosphorylation was significantly higher in the high-Skp2-expression group compared with the low- Skp2-expression group (P = 0.035). The Skp2 overexpression was significantly associated with shorter disease-free survival and overall survival (P = 0.0386 and P = 0.0369, respectively). Multivariate analysis showed that Skp2 expression was an independent prognostic factor both in the disease-free survival and overall survival. CONCLUSION: These findings suggest that Skp2 expression is an independent marker for a poor prognosis in AML. The presence of a positive correlation between Skp2 and phosphorylated PTEN suggests that an aberration in the PTEN/Skp2 signaling pathway might be operating in AML.
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1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ko, Yun Woong(고윤웅)
Kim, Ji Yeon(김지연)
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Lee, Seung Tae(이승태)
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
Hahn, Jee Sook(한지숙)
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