Pathogenesis of prolactinomas.
In recent years the demonstration that human pituitary adenomas are monoclonal in origin provides further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. However, with the exception of one RAS mutation identified in a single unusually aggressive prolactinoma resistant to dopaminergic inhibition that resulted to be lethal, no mutational changes have been so far detected in prolactinomas. In the absence of genetic changes, modifications in the level of expression of oncogenes or tumor suppressor genes have been detected in these tumors, although it is unknown whether these changes have a causative role or are a secondary event. Indeed, our knowledge on the molecular events involved in lactotroph proliferation is even more limited in comparison to the other tumor types, since these tumors are very infrequently surgically removed and therefore available for molecular biology studies. In this respect, it is worth noting that the molecular and biological abnormalities so far described in prolactinomas mainly concern aggressive and atypical tumors and likely do not apply to the typical prolactinomas, that are characterized by good response to medical treatment and a very low growth rate.
Spada
Anna
A
Institute of Endocrine Sciences, Ospedale Maggiore IRCCS, University of Milan, 20122, Milano, Italy.
Mantovani
Giovanna
G
Lania
Andrea
A
D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000235:genetics / Q000502:physiology; D006801:Humans; D009154:Mutation; D010911:Pituitary Neoplasms / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D015175:Prolactinoma / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D011519:Proto-Oncogenes
D004273:DNA, Neoplasm; D006133:Growth Substances