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Molecular genetics of adrenocortical tumor formation and potential pharmacologic targets

M Rauschecker1, C A Stratakis

  • 1Program of Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), National Inastitutes of Health (NIH), Bethesda, Maryland 20892, USA. rauscheckerm@mail.nih.gov

Minerva Endocrinologica
|June 14, 2012
PubMed

Insights

Adrenal tumors involve cAMP/PKA and Wnt signaling pathways. Understanding these molecular genetics may lead to targeted pharmacologic therapies for adrenal cortex tumors.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Abnormalities in the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway are linked to benign adrenal tumors and a predisposition to adrenocortical cancer.
  • Mutations in G-protein coupled receptors and defects in cAMP-dependent protein kinase A are associated with various adrenal hyperplasias and syndromes.
  • Defects in phosphodiesterases and the Wnt signaling pathway also play roles in adrenocortical tumorigenesis.

Purpose of the Study:

  • To review the molecular genetics of adrenocortical tumors.
  • To identify potential targets for pharmacologic therapy in adrenocortical tumorigenesis.

Main Methods:

  • Review of molecular genetics literature concerning adrenocortical tumors.
  • Analysis of signaling pathways implicated in adrenal tumor formation, including cAMP/PKA and Wnt pathways.
  • Inclusion of microRNA profiling data.

Main Results:

  • Specific genetic mutations and pathway defects identified in various benign and malignant adrenal tumors.
  • Implication of cAMP/PKA, G-protein coupled receptors, phosphodiesterases, and Wnt signaling in adrenal tumorigenesis.
  • MicroRNA profiling provides further insight into molecular mechanisms.

Conclusions:

  • The molecular understanding of adrenocortical tumors is advancing through genetic and pathway analysis.
  • Potential pharmacologic targets for therapy are emerging from this research.
  • Further investigation is warranted to translate these findings into clinical treatments.

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