Isozyme-specific abnormalities of PKC in thyroid cancer: evidence for post-transcriptional changes in PKC epsilon.
PKC isozymes are the major binding proteins for tumor-promoting phorbol esters, and PKC activity is abnormal in a number of different human cancers. Less is known about putative structural and functional changes of specific PKC isozymes in human neoplasms. A single-point mutation of PKCalpha at position 881 of the coding sequence has been observed in human pituitary adenomas and up to 50% of thyroid follicular neoplasms, and a rearrangement of PKCepsilon was reported in a thyroid follicular carcinoma cell line, suggesting that these signaling proteins may play a role in thyroid tumorigenesis. To explore this possibility, we examined thyroid neoplasms for mutations and changes in expression levels of PKCepsilon or alpha. None of the 57 follicular adenomas, 26 papillary carcinomas (PCs), 7 follicular carcinomas, or the anaplastic carcinoma harbored the PKCalpha 881A>G mutation. Moreover, none of 15 PCs, 10 follicular adenomas, or 6 follicular carcinomas showed evidence of mutations of PKCepsilon. However, 8 of 11 PCs had major isozyme-specific reductions of the PKCepsilon protein, which occurred through either translational or posttranslational mechanisms. These data indicate that post-transcriptional changes in PKCepsilon are highly prevalent in thyroid tumors and may play a significant role in their development.
Knauf
Jeffrey A
JA
Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Ward
Laura S
LS
Nikiforov
Yuri E
YE
Nikiforova
Marina
M
Puxeddu
Efisio
E
Medvedovic
Mario
M
Liron
Tamar
T
Mochly-Rosen
Daria
D
Fagin
James A
JA
D000236:Adenoma / Q000201:enzymology / Q000235:genetics; D000483:Alleles; D015139:Blotting, Southern; D015153:Blotting, Western; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics; D002291:Carcinoma, Papillary / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D009693:Nucleic Acid Hybridization; D018807:Polymorphism, Single-Stranded Conformational; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics*
D007527:Isoenzymes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C496628:PRKCA protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon