title: Phosphodiesterase function and endocrine cells: links to human disease and roles in tumor development and treatment.
abstract: Phosphodiesterases (PDEs) are enzymes that regulate the intracellular levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate, and, consequently, exhibit a central role in multiple cellular functions. The pharmacological exploitation of the ability of PDEs to regulate specific pathways has led to the discovery of drugs with selective action against specific PDE isoforms. Considerable attention has been given to the development of selective PDE inhibitors, especially after the therapeutic success of PDE5 inhibitors in the treatment of erectile dysfunction. Several associations between PDE genes and genetic diseases have been described, and more recently PDE11A and PDE8B have been implicated in predisposition to tumor formation. This review focuses on the possible function of PDEs in a variety of tumors, primarily in endocrine glands, both in tumor predisposition and as potential therapeutic targets.
authors: Section of Endocrinology and Genetics, Program on Developmental Endocrinology Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. levyi2@mail.nih.gov
authors: Isaac
authors: I
authors: Levy
authors: Anelia
authors: A
authors: Horvath
authors: Monalisa
authors: M
authors: Azevedo
authors: Rodrigo Bertollo
authors: RB
authors: de Alexandre
authors: Constantine A
authors: CA
authors: Stratakis
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000502:physiology; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000502:physiology; D055098:Endocrine Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004701:Endocrine Gland Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007527:Isoenzymes; D009363:Neoplasm Proteins; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP