title: Tumor suppressor loss in pituitary tumors.
abstract: The current model of human neoplasia invokes a number of potential genomic alterations that impact cellular phenotype and proliferative rates. In the majority of human tumor models, the transformation from normal cells to neoplastic lesion is a multistep process. This review offers a specific overview of the involvement of tumor suppressor genes (TSGs) in the pathogenesis of human pituitary adenomas. TSG genetic lesions, such as BRCA1 in breast cancer and p53 in Li-Fraumeni Syndrome, have been identified in both sporadic and heritable human endocrine tumors. Familial neoplastic syndromes like multiple endocrine neoplasia type 1 (MEN1) that include pituitary tumor formation as part of a broad clinical spectrum of disease represent a unique opportunity to investigate the general mechanisms of tumorigenesis, and well as genes responsible for sporadic endocrine tumors. Similarly, homologous recombination knockout mice with selectively ablated candidate TSGs have also shed light on the molecular mechanisms of pituitary cell proliferation and tumor suppression. However, despite insights into pituitary tumorigenesis generated by heritable neoplasia syndromes and mouse knockout of critical TSGs that display a pituitary tumor phenotype, the molecular pathogenesis of human pituitary adenomas remains largely an enigma. Thus, the role of TSGs, if any, in sporadic pituitary adenoma formation has yet to be determined, despite our greater understanding of the molecular mechanisms underlying pituitary cell function and phenotype.
authors: Harvard Medical School, Boston, MA, USA. jalexand@caregroup.harvard.edu
authors: J M
authors: JM
authors: Alexander
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D005260:Female; D017353:Gene Deletion; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018598:Minisatellite Repeats; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics; D006623:von Hippel-Lindau Disease / Q000235:genetics
chemical_list: C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D019382:Human Growth Hormone; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases