Pituitary tumour transforming gene: a novel factor in pituitary tumour formation

Although pituitary tumours are common monoclonal neoplasms, they rarely metastasize outside the pituitary fossa, even though they cause considerable morbidity and mortality. Many molecular events underlying pituitary tumourigenesis have been elucidated in recent years, but no clear tumour marker has emerged that assists clinical decision-making with regard to appropriate therapy. Activating mutations and a loss of inactivating mutations, together with hypothalamic hormones, circulating hormones, growth factors and cytokines, co-operatively ensure the inexorable expansion of the initial mutated pituitary cell clone. We have recently described a novel oestrogen-regulated activating oncogene, pituitary tumour transforming gene (PTTG), which is potently transforming in vitro and in vivo, regulates basic fibroblast growth factor secretion and inhibits chromatid separation. In experimental animal pituitary tumour models, increased PTTG expression occurs early in cell transformation (from normal to hyperplastic cell), PTTG overexpression being observed in 99% of pituitary tumours. PTTG presents an attractive target for designing subcellular pituitary tumour therapy, and an increased understanding of its role and that of other genetic events in pituitary tumorigenesis may provide novel approaches to pituitary tumour management.