ISSN:
0730-2312
Keywords:
human hepatoma
;
dedifferentiation/progression
;
PDPK
;
overexpression
;
kinase FA/GSK-3α
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Computer analysis of protein phosphorylation sites sequence revealed that transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of the proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3α (kinase FA/GSK-3α) (a member of PDPK family) has been optimized for human hepatoma and used to demonstrate for the first time significantly increased (P 〈 0.01) activity in poorly differentiated SK-Hep-1 hepatoma (24.2 ± 2.8 units/mg) and moderately differentiated Mahlavu hepatoma (14.5 ± 2.2 units/mg) when compared to well differentiated Hep 3B hepatoma (8.0 ± 2.4 units/mg). Immunoblotting analysis revealed that increased activity of kinase FA/GSK-3α is due to overexpression of the protein. Elevated kinase FA/GSK-3α expression in human hepatoma biopsies relative to normal liver tissue was found to be even more profound. This kinase appeared to be ∼fivefold overexpressed in well differentiated hepatoma and ∼13-fold overexpressed in poorly differentiated hepatoma when compared to normal liver tissue. Taken together, the results provide initial evidence that overexpression of kinase FA/GSK-3α is involved in human hepatoma dedifferentiation/progression. Since kinase FA/GSK-3α is a PDPK, the results further support a potential role of this kinase in human liver tumorigenesis, especially in its dedifferentiation/progression. © 1996 Wiley-Liss, Inc.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
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