Document Detail


Nuclear translocation of survivin in hepatocellular carcinoma: a key to cancer cell growth?
MedLine Citation:
PMID:  14652813     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Survivin is a recently described anti-apoptosis protein and regulator of cell division. Its expression and localization in hepatocellular carcinoma (HCC) and in normal liver tissue has not been fully elucidated. We examined the expression of survivin, Fas, proliferating cell nuclear antigen (PCNA), and apoptosis in 47 specimens of hepatocellular carcinoma (HCC) and surrounding nonmalignant hepatic tissues. To further determine the relationship between survivin expression and cell proliferation and apoptosis, we performed double immunostaining for survivin and PCNA TUNEL staining in the same HCC specimens. Positive immunostaining for survivin was present in 35 of 47 (74%) HCCs. Twenty-two of 35 survivin-positive HCCs (63%) showed punctate nuclear staining in HCC cells, and the remaining 13 showed predominant cytoplasmic staining. In contrast, nonmalignant hepatocytes showed only cytoplasmic staining. HCC cells had significantly higher PCNA-labeling and apoptotic indices compared with the case of nonmalignant hepatic tissue (P<0.001). Furthermore, nucleus-positive HCC specimens for survivin showed the highest PCNA labeling index. The nuclear localization of survivin in HCC cells correlated with tumor cell de-differentiation with the exception of the HepG2 cell line. Survivin expression was inversely associated with apoptosis and was strongly associated with Fas expression (P=0.01). All 4 HCC cell lines examined showed survivin expression and punctate nuclear localization. Our results indicate that survivin is localized to the cytoplasm in quiescent nonmalignant liver cells to suppress apoptosis and translocates into the nucleus in HCC cells. In conclusion, translocation of survivin from the cytoplasm to the nucleus may constitute an important regulatory mechanism for cell proliferation and differentiation in HCC.
Authors:
Woo Sung Moon; Andrzej S Tarnawski
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Human pathology     Volume:  34     ISSN:  0046-8177     ISO Abbreviation:  Hum. Pathol.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-12-03     Completed Date:  2004-01-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421547     Medline TA:  Hum Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1119-26     Citation Subset:  IM    
Affiliation:
Department of Medicine, Veterans Administration Medical Center, Long Beach, CA 90822, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antigens, CD95 / metabolism
Apoptosis / physiology*
Blotting, Western
Carcinoma, Hepatocellular / metabolism,  pathology*
Cell Division / physiology
Cell Nucleus / metabolism
Cell Transformation, Neoplastic / metabolism*
Cytoplasm / metabolism
Female
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Liver Neoplasms / metabolism,  pathology*
Male
Microtubule-Associated Proteins / metabolism*
Middle Aged
Neoplasm Proteins
Proliferating Cell Nuclear Antigen / metabolism
Protein Transport / physiology
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/BIRC5 protein, human; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Proliferating Cell Nuclear Antigen

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