Pituitary tumour-transforming gene (PTTG) and pituitary senescence.
Pituitary tumours account for 15% of intracranial neoplasms and are benign monoclonal neoplasms that may be clinically silent or secrete hormones, including prolactin, growth hormone, adrenocorticotrophic hormone or, rarely, thyroid-stimulating hormone or gonadotrophins. These adenomas account for clinical infertility, growth disorders and hypercortisolism or metabolic dysfunctions associated with hypopituitarism. We explored the role of disordered pituitary cell proliferation control in the pathogenesis of these invariably benign adenomas, studying the mechanisms underlying pituitary aneuploidy, premature proliferative arrest (senescence), markers of cell proliferation and tumorigenesis in single, double or triply mutant transgenic mice with mutations of Rb, Pttg and/or p21. Our results provide further insights into the role of cell-cycle control and growth constraints on experimental and human pituitary tumours, which underlie their failure to progress to malignancy. These results improve our understanding of pituitary syndromes associated with infertility, growth disorders, hypercortisolism or adrenal, thyroid and gonadal failure due to abrogated pituitary function.
Chesnokova
Vera
V
Cedars-Sinai Medical Center, David Geffen School of Medicine, Los Angeles, CA 90048, USA.
Melmed
Shlomo
S
D000308:Adrenocortical Hyperfunction / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D000782:Aneuploidy; D000818:Animals; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D002453:Cell Cycle; D016922:Cellular Senescence; D006130:Growth Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007246:Infertility / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D064249:Securin
D009363:Neoplasm Proteins; D010907:Pituitary Hormones; D016160:Retinoblastoma Protein; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human