Elevated activities of protein kinase C and tyrosine kinase correlate to leukemic cell aggressiveness.
We report a linkage between cell aggressiveness, protein kinase C (PKC) activity, tyrosine kinase (PTK) activity and serum requirement. We used 2 leukemic cell lines induced by Moloney murine leukemia virus (MLV). One line was highly aggressive (BS-24-1) and required low serum concentrations (3%) for optimal growth in comparison to the less aggressive line (RO2T) that needed 10% serum for optimal growth. The more malignant cells exhibited higher PKC and PTK activity. This activity was independent of serum concentration between 0.01-10%. In contrast, the weakly malignant cells need a high serum concentration (10%) for optimal PKC or PTK activity. Immunoblot analysis revealed a higher level of PKC protein in the BS-24-1 cells than in the RO2T cells. Serum induction of PKC activity did not change the amount of PKC protein in the cytosol or the membrane fractions, indicating post-translational mechanism regulation of PKC. We suggest that the aggressiveness of BS-24-1 resulted from its ability to become independent of growth regulation by serum factors, via autocrine stimulation of PKC and PTK.
Aflalo
E
E
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Wolfson
M
M
Ofir
R
R
Weinstein
Y
Y
D000818:Animals; D002451:Cell Compartmentation; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D016895:Culture Media, Serum-Free; D003600:Cytosol / Q000201:enzymology; D006133:Growth Substances / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D006133:Growth Substances; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate