Expression of protein kinase A regulatory subunits in benign and malignant human thyroid tissues: A systematic review

Alessandro Del Gobbo, Erika Maria Peverelli, D. Treppiedi, Andrea Gerardo Antonio Lania, Giovanna Mantovani, Stefano Ferrero

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalExperimental Cell Research
DOIs
Publication statusAccepted/In press - Mar 18 2016

Keywords

  • Carney complex
  • Follicular carcinoma
  • Medullary carcinoma
  • Nodular hyperplasia
  • PKA
  • Thyroid

ASJC Scopus subject areas

  • Cell Biology

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