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Isozyme-Specific Abnormalities of PKC in Thyroid Cancer: Evidence for Post-Transcriptional Changes in PKC Epsilon

Division of Endocrinology and Metabolism (J.A.K., L.S.W., Y.E.N., M.N., E.P., J.A.F.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45267; Department of Environmental Health (M.M.), University of Cincinnati, Cincinnati, Ohio 45267; and Department of Molecular Pharmacology (T.L., D.M.-R.), Stanford University School of Medicine, Stanford, California 94305

Address all correspondence and requests for reprints to: Jeffrey A. Knauf, Ph.D., Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, P.O. Box 670547, Cincinnati, Ohio 45267-0547. E-mail: . jeffrey.knauf{at}uc.edu

Abstract

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 PKC 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 PKC 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 PKC or . None of the 57 follicular adenomas, 26 papillary carcinomas (PCs), 7 follicular carcinomas, or the anaplastic carcinoma harbored the PKC 881A>G mutation. Moreover, none of 15 PCs, 10 follicular adenomas, or 6 follicular carcinomas showed evidence of mutations of PKC. However, 8 of 11 PCs had major isozyme-specific reductions of the PKC protein, which occurred through either translational or posttranslational mechanisms. These data indicate that post-transcriptional changes in PKC are highly prevalent in thyroid tumors and may play a significant role in their development.

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