Expression of protein kinase A regulatory subunits in benign and malignant human thyroid tissues: A systematic review.
In this review, we discuss the molecular mechanisms and prognostic implications of the protein kinase A (PKA) signaling pathway in human tumors, with special emphasis on the malignant thyroid. The PKA signaling pathway is differentially activated by the expression of regulatory subunits 1 (R1) and 2 (R2), whose levels change during development, differentiation, and neoplastic transformation. Following the identification of gene mutations within the PKA regulatory subunit R1A (PRKAR1A) that cause Carney complex-associated neoplasms, several investigators have studied PRKAR1A expression in sporadic thyroid tumors. The PKA regulatory subunit R2B (PRKAR2B) is highly expressed in benign, as well as in malignant differentiated and undifferentiated lesions. PRKAR1A is highly expressed in follicular adenomas and malignant lesions with a statistically significant gradient between benign and malignant tumors; however, it is not expressed in hyperplastic nodules. Although the importance of PKA in human malignancy outcomes is not completely understood, PRKAR1A expression correlates with tumor dimension in malignant lesions. Additional studies are needed to determine whether a relationship exists between PKA subunit expression and clinical outcomes, particularly in undifferentiated tumors. In conclusion, the R1A subunit might be a good molecular candidate for the targeted treatment of malignant thyroid tumors.
Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Alessandro
A
Del Gobbo
Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Erika
E
Peverelli
Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Donatella
D
Treppiedi
Endocrine Unit, IRCCS Humanitas Research Hospital, University of Milan, Milan, Italy.
Andrea
A
Lania
Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Giovanna
G
Mantovani
Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan Medical School, Milan, Italy. Electronic address: stefano.ferrero@unimi.it.
Stefano
S
Ferrero
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D021122:Protein Subunits / Q000378:metabolism*; D013961:Thyroid Gland / Q000201:enzymology* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000473:pathology*
D021122:Protein Subunits; D017868:Cyclic AMP-Dependent Protein Kinases
Carney complex; Follicular carcinoma; Medullary carcinoma; Nodular hyperplasia; PKA; Thyroid