[Molecular aspects of pituitary tumors].
Pituitary adenomas are common benign neoplasms, accounting for approximately 15% of intracranial tumors. In systematic autopsy, pituitary tumors are found in 25%, of the population, but only one-third of these tumors give rise to clinical manifestations. Why most of these neoplasms remain undiagnosed and pituitary carcinomas are extremely rare? The progress in the studies concerning pituitary tumorigenesis is rather slow and, due to several limitations, including the anatomic inaccessibility of human pituitary gland, the lack of functional human cell lines in culture and the discrepancies between human and animal pituitary oncogenesis (in rodents pituitary hyperplasia is a prerequisite for adenoma development). In humans, the majority of pituitary tumors are monoclonal in origin and derived from single mutated pituicyte, rarely hyperplasia is a prerequisite for adenoma formation. As in the case of other tumors, activating mutations in oncogenes (GNAS1, PTTG) and inactivating mutations in tumor suppressor genes (MEN1, CNC1) lead to pituitary tumors development. However, mutations in classic oncogenes are very rarely associated with these tumors. Moreover, the important role of some hypothalamic hormones, peripheral hormones and their receptors (e.g. GHRH, dopamine D2 receptor, PRL receptor, estrogens, thyroid hormone receptor) and growth factors (e.g. FGF, EGF, TGF) is postulated and partially proved in promotion of pituitary tumorigenesis. Further studies are required to determine which of these events are truly primary changes in pituitary tumorigenesis, what may allow development of gene therapy.
Mełeń-Mucha
Gabriela
G
Department of Experimental Endocrinology and Hormone Diagnostics, Institute of Endocrinology, Medical University of Lodz. g.m-mucha@wp.pl
D000818:Animals; D002864:Chromogranins; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases; D019205:GTP-Binding Protein alpha Subunits, Gs; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins; D010911:Pituitary Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D011506:Proteins; D011518:Proto-Oncogene Proteins; D064249:Securin
D002864:Chromogranins; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; C517834:PRKAR1A protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D017868:Cyclic AMP-Dependent Protein Kinases; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs