論文

査読有り
2003年8月

Loss of p16 contributes to p27 sequestration by cyclin D-1-cyclindependent kinase 4 complexes and poor prognosis in hepatocellular carcinoma

CLINICAL CANCER RESEARCH
  • Y Matsuda
  • ,
  • T Ichida
  • ,
  • T Genda
  • ,
  • S Yamagiwa
  • ,
  • Y Aoyagi
  • ,
  • H Asakura

9
9
開始ページ
3389
終了ページ
3396
記述言語
英語
掲載種別
研究論文(学術雑誌)
出版者・発行元
AMER ASSOC CANCER RESEARCH

Purpose: p27(Kipl) (p27) might act as an adverse prognostic marker for various types of cancers. However, its clinical usefulness remains uncertain, because it is sometimes overexpressed in aggressive types.
Experimental Design: To precisely evaluate the practical significance of p27 in hepatocellular carcinoma (HCC), we immunohistochemically compared the level of p27 expression with Ki-67 labeling in 74 HCCs and focused on tumors in which cell proliferation increased despite a high level of p27 expression. We then analyzed the status of p27 and related cell-cycle regulators using kinase and immuno-precipitation assays, Western blotting, and methylation-specific PCR to understand the rationale for the functional inactivation of p27 in HCC. We also evaluated relationships between the key biological characteristics of HCC and survival.
Results: Immunohistochemical studies showed that 40 (54%) of 74 HCCs expressed high levels of p27 (>50% of the tumor cells). Of these, the Ki-67 labeling index was low (<20%) in 26 (65%) and high (>20%) in 14 (35%). Increased proliferative activities were closely correlated with elevated kinase activities, sequestration of p27 protein, and p16 gene methylation. The association between a loss of p16 and poor prognosis was significant when p27 expression was high (P < 0.01).
Conclusions: The loss of p16 appears to be closely related to the functional inactivation of p27, and assessment of p16 status may be useful for a precise prognostic prediction of individuals with HCC expressing high levels of p27.

リンク情報
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/12960127
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000185172600022&DestApp=WOS_CPL
ID情報
  • ISSN : 1078-0432
  • PubMed ID : 12960127
  • Web of Science ID : WOS:000185172600022

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