β-Catenin stimulates pituitary stem cells to form aggressive tumors

Abstract

Pituitary adenomas are common in older people, representing approximately 10% of intracranial neoplasias (1). They tend to be slow-growing, and are usually benign, but they can compress the brain and optic chiasm and cause abnormalities in pituitary hormone production. A fraction of pituitary adenomas become invasive and are resistant to treatment with surgery, radiation, and pharmacotherapy. Progress is being made in identification of genes that enhance the risk of pituitary adenoma formation, but the etiology of many adenomas remains unexplained (1, 2). Common adenomas are sporadic and clonal in origin. Craniopharyngiomas differ from most sporadic pituitary adenomas in that they occur in children, tend to be resistant to treatment, and cause significant morbidity. Histopathology analyses suggested that craniopharyngiomas arise from embryonic pituitary tissue and implicated β-catenin as a marker. In PNAS, Gaston-Massuet and colleagues provide proof that craniopharyngiomas arise from activation of β-catenin in pituitary progenitors during embryogenesis (3). Their elegant studies in patient tumor samples and genetically engineered mice lend support to the cancer stem cell hypothesis. They also provide insight into the basic nature of pituitary progenitors, the stem cell niche, and normal regulation of the transition from self-renewal to differentiation. Now the pituitary gland joins a collection of other tissues in which β-catenin signaling can affect this critical decision point (4).