Linked Life Data

19350262

Source:http://linkedlifedata.com/resource/pubmed/id/19350262

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-6-9
pubmed:abstractText
Hepatocellular carcinoma (HCC) represents the sixth most frequent human cancer worldwide and is characterized by rapid progression as well as resistance to systemic chemotherapy. Recently, glycolysis has emerged as a potent driving force of tumor growth and therapy failure. The precise role of glycolysis for the pathogenesis of human HCC has not been elucidated thus far. Therefore, we have conducted a comprehensive analysis of the expression patterns of central glycolysis-related factors [glucose transporter-1 and -2 (Glut-1 and Glut-2), phosphoglycerate kinase-1 (PGK-1) and hypoxia-inducible factor-1alpha (HIF-1alpha)] in a large cohort of benign and malignant human liver samples. PGK-1 protein and gene expression was scant in normal liver, elevated in cirrhotic livers and most intense in HCC. Strong immunoreactivity of Glut-2 was noted in cirrhotic livers, whereas in HCC it was only expressed in 50% of examined cases. Strikingly, PGK-1 as well as Glut-2 protein expression was indicative of poor patient prognosis. Glut-1 protein was absent in neoplastic hepatocytes but prominent in tumor-associated endothelial cells. Specific nuclear staining of HIF-1alpha was noted in only 12% of HCC samples. Our data point toward a tumor-promoting function of glycolysis in HCC and establish PGK-1 as an independent prognostic parameter. Furthermore, the endothelial-specific expression of Glut-1 makes a special dependence of vessels on glucose reasonable to assume. In summary, we believe our analysis warrants the validation of glycolytic inhibitors as innovative treatment approaches of human HCC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1432-119X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21-31
pubmed:meshHeading
pubmed-meshheading:19350262-Adolescent, pubmed-meshheading:19350262-Adult, pubmed-meshheading:19350262-Aged, pubmed-meshheading:19350262-Aged, 80 and over, pubmed-meshheading:19350262-Carcinoma, Hepatocellular, pubmed-meshheading:19350262-Endothelium, Vascular, pubmed-meshheading:19350262-Female, pubmed-meshheading:19350262-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19350262-Glucose Transporter Type 1, pubmed-meshheading:19350262-Glucose Transporter Type 2, pubmed-meshheading:19350262-Glycolysis, pubmed-meshheading:19350262-Hepatocytes, pubmed-meshheading:19350262-Humans, pubmed-meshheading:19350262-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:19350262-Immunohistochemistry, pubmed-meshheading:19350262-Liver Neoplasms, pubmed-meshheading:19350262-Male, pubmed-meshheading:19350262-Middle Aged, pubmed-meshheading:19350262-Neoplasm Proteins, pubmed-meshheading:19350262-Phosphoglycerate Kinase, pubmed-meshheading:19350262-Young Adult
pubmed:year
2009
pubmed:articleTitle
Distinct temporospatial expression patterns of glycolysis-related proteins in human hepatocellular carcinoma.
pubmed:affiliation
Medizinische Klink mit Schwerpunkt Hepatologie und Gastroenterologie, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't