Plasma protein kinase C (PKC)alpha as a biomarker for the diagnosis of cancers.
Protein kinase C (PKC)alpha plays a key role in the differentiation, proliferation and apoptosis of cancer cells, and its activity is higher in cancer cells than in normal cells. In the present study, we investigated the existence of activated PKCalpha in plasma and its possibility for cancer diagnosis. Plasma samples were prepared from xenograft mouse models of cancer and from normal mice. Phosphorylation ratios for a PKCalpha-specific peptide substrate (Alphatomega) were analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry and activated PKCalpha was identified by western blot analysis. Increased levels of activated PKCalpha were found in the plasma of cancer-bearing mice (U87, A549, A431, HuH-7 and B16 melanoma) compared with the levels found in control mice. Phosphorylation ratios for peptide substrate increased with an increase in tumor size. Moreover, the addition of Ro-31-7549, a highly specific inhibitor of PKCalpha, produced a concentration-dependent reduction of phosphorylation ratios, whereas the non-PKCalpha inhibitors, rottlerin and H-89, did not significantly effect phosphorylation ratios. In addition, the level of activated PKCalpha decreased after cancer resection but increased if the cancer recurred. From these results, we suggest that (i) activated PKCalpha in plasma can be a useful biomarker for the diagnosis of cancers and (ii) the level of activated PKCalpha can be monitored to assess the recurrence of cancer after surgical removal. To our knowledge, this is the first report demonstrating the existence of activated PKCalpha in plasma and its possibility for cancer diagnosis.
Kang
Jeong-Hun
JH
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka 819-0395, Japan. jrjhkang@ri.ncvc.go.jp
Asai
Daisuke
D
Toita
Riki
R
Kitazaki
Hirotaro
H
Katayama
Yoshiki
Y
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000097:blood*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D000098:Acetophenones; D001578:Benzopyrans; D014408:Biomarkers, Tumor; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C085746:rottlerin; D051571:Protein Kinase C-alpha; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C064755:Ro 31-7549