title: Molecular genetics of the cAMP-dependent protein kinase pathway and of sporadic pituitary tumorigenesis.
abstract: Pituitary tumors are among the most common human neoplasms. Although these common lesions rarely become clinically manifest and they are almost never malignant, they are the cause of significant morbidity in affected patients. The genetic causes of common pituitary tumors remain for the most part unknown; progress has been limited to the elucidation of the molecular etiology of four genetic syndromes predisposing to pituitary neoplasias: McCune-Albright syndrome, multiple endocrine neoplasia type 1, Carney complex and, most recently, familial acromegaly and prolactinomas and other tumors caused by mutations in the GNAS, menin, PRKAR1A, AIP, and p27 (CDKN1B) genes, respectively. Intense molecular studies of sporadic pituitary tumors from patients with negative family histories and no other neoplasms have yielded interesting findings with abnormalities in growth factor expression and cell cycle control dysregulation. To add to the difficulties in understanding pituitary tumorigenesis in man, good murine models of these neoplasms simply do not exist: pituitary tumors are common in rodents, but their histologic origin (mostly from the intermediate lobe), age of presentation (late in murine life) and clinical course make them hardly models of their human counterparts. The present report reviews the clinical and molecular genetics of the cAMP-dependent protein kinase pathway in human pituitary tumors; it also reviews briefly other pathways that have been involved in sporadic pituitary neoplasms. At the end, we attempt a unifying hypothesis for pituitary tumorigenesis, taking into account data that are also discussed elsewhere in this issue.
authors.affiliation: Section on Endocrinology and Genetics (SEGEN), Developmental Endocrinology Branch (DEB), National Institute of Child Health and Human Development (NICHD), National Institues of Health, Bethesda, MD 20892-1103, USA.
authors.forename: Sosipatros A
authors.initials: SA
authors.lastname: Boikos
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008967:Molecular Biology; D009363:Neoplasm Proteins / Q000235:genetics; D010911:Pituitary Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017978:Receptors, Growth Factor / Q000235:genetics; D064249:Securin; D015398:Signal Transduction; D013577:Syndrome
chemical_list: D006133:Growth Substances; D009363:Neoplasm Proteins; D017978:Receptors, Growth Factor; D064249:Securin; D017868:Cyclic AMP-Dependent Protein Kinases