The pathophysiology of pituitary adenomas.
The pathogenesis of tumour formation in the anterior pituitary has been intensively studied, but the causative mechanisms involved in pituitary cell transformation and tumourigenesis remain elusive. Most pituitary tumours are sporadic, but some arise as a component of genetic syndromes such as the McCune-Albright syndrome, multiple endocrine neoplasia type 1, Carney complex and, the most recently described, a MEN1-like phenotype (MEN4) and pituitary adenoma predisposition syndromes. Some specific genes have been identified that predispose to pituitary neoplasia (GNAS, MEN1, PRKAR1A, CDKN1B and AIP), but these are rarely involved in the pathogenesis of sporadic tumours. Mutations of tumour suppressor genes or oncogenes, as seen in more common cancers, do not seem to play an important role in the great majority of pituitary adenomas. The pituitary tumour transforming gene (PTTG; securin) was the first transforming gene found to be highly expressed in pituitary tumour cells, and seems to play an important role in the process of oncogenesis. Many tumour suppressor genes, especially those involved in the regulation of the cell cycle, are under-expressed, most often by epigenetic modulation - usually promoter hypermethylation - but the regulator of these co-ordinated series of methylations is also unclear. Cell signalling abnormalities have been identified in pituitary tumours, but their genetic basis is unknown. Both Raf/MEK/ERK and PI3K/Akt/mTOR pathways are over-expressed and/or over-activated in pituitary tumours: these pathways share a common root, including initial activation related to the tyrosine kinase receptor, and we speculate that a change to these receptors or their relationship to membrane matrix-related proteins may be an early event in pituitary tumourigenesis.
Dworakowska
Dorota
D
Centre for Endocrinology, Barts and the London School of Medicine, EC1M 6BQ, UK.
Grossman
Ashley B
AB
D000236:Adenoma / Q000209:etiology* / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D009857:Oncogenes / Q000502:physiology; D010911:Pituitary Neoplasms / Q000209:etiology* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013577:Syndrome
D036341:Intercellular Signaling Peptides and Proteins