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
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- 巻
- 9
- 号
- 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.
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
- ID情報
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- ISSN : 1078-0432
- PubMed ID : 12960127
- Web of Science ID : WOS:000185172600022