Regulatory Subunit Type 1- alpha of Protein Kinase A (PRKARIA): A Tumor-Suppressor Gene for Sporadic Thyroid Cancer

The tumor-suppressor gene encoding the cyclic AMP-dependent protein kinase A type 1- alpha regulatory subunit PRKARIA has been mapped to chromosome 17 (17q22-24) and is mutated in Carney complex, a familial neoplasia syndrome that is associated with thyroid tumors. Other genes implicated in cyclic n...

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Bibliographic Details
Published in:Genes chromosomes & cancer 2002-10, Vol.35 (2), p.182-192
Main Authors: Sandrini, F, Matyakhina, L, Sarlis, N J, Kirschner, L S, Farmakidis, C, Gimm, O, Stratakis, CA
Format: Article
Language:English
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Summary:The tumor-suppressor gene encoding the cyclic AMP-dependent protein kinase A type 1- alpha regulatory subunit PRKARIA has been mapped to chromosome 17 (17q22-24) and is mutated in Carney complex, a familial neoplasia syndrome that is associated with thyroid tumors. Other genes implicated in cyclic nucleotide-dependent signaling have been investigated in thyroid tumorigenesis. We studied protein kinase A (PKA) activity in noninherited follicular thyroid adenomas and follicular, papillary, and undifferentiated (anaplastic) thyroid carcinomas. We then examined these and additional thyroid tumors for losses of the 17q22-24 PRKARIA region, mutations of the PRKARIA gene, and expression of its peptide product. Total PKA activity was markedly increased in carcinomas over that in adenomas, whereas the ratio of free vs. total PKA activity was decreased in cancer. Consistent with these findings, the 17q22-24 region was frequently lost in cancer but not in benign adenomas. A novel inactivating mutation of the PRKARIA gene (leading to premature termination of the predicted protein) was found in an aggressive thyroid cancer. The tumor with PRKARIA gene mutation, as well as the tumors with 17q allelic losses, showed decreased PRKARIA expression by immunostaining. We conclude that PRKARIA, the most abundant regulatory subunit of protein kinase A and a principal cyclic AMP-signaling modulator, acts as a tumor-suppressor gene in sporadic thyroid cancer.
ISSN:1045-2257
DOI:10.1002/gcc.10112