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

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