How Could Mutated AIP Lead to Formation of a Pituitary Tumor?
Because intrapituitary cAMP abundance is vital for controlling both cell replication and hormone synthesis (35), disrupted AIP could lead to elevated cAMP levels and hence promote tumor formation. This hypothesis requires rigorous in vitro and in vivo testing and will certainly add important insights into the biology of pituitary adenomas. The R304X mutation results in disrupted AHR binding, and a recent report has shown that immunoreactive AIP is indeed less abundant in pituitary tumor tissue that exhibits LOH for AIP (30). The observed loss of the wild-type allele in mutation-positive tumors suggests that they are truly null for AIP. This evidence lends credence to the notion that the AIP gene product may exhibit characteristics of a tumor suppressor protein. The studies thus far reported indicate the presence of AIP germ line mutations in a small (15%) subset of a very rare Mendelian disorder. Several important sets of experiments are required to satisfy the postulate that AIP disru
Because intrapituitary cAMP abundance is vital for controlling both cell replication and hormone synthesis (35), disrupted AIP could lead to elevated cAMP levels and hence promote tumor formation. This hypothesis requires rigorous in vitro and in vivo testing and will certainly add important insights into the biology of pituitary adenomas. The R304X mutation results in disrupted AHR binding, and a recent report has shown that immunoreactive AIP is indeed less abundant in pituitary tumor tissue that exhibits LOH for AIP (30). The observed loss of the wild-type allele in mutation-positive tumors suggests that they are truly null for AIP. This evidence lends credence to the notion that the AIP gene product may exhibit characteristics of a tumor suppressor protein. The studies thus far reported indicate the presence of AIP germ line mutations in a small (∼15%) subset of a very rare Mendelian disorder. Several important sets of experiments are required to satisfy the postulate that AIP disr
