Molecular pathogenesis of pituitary adenomas: A review

Modern theory of tumorigenesis suggests that genetic alterations may play a role in the initiation and promotion of pituitary adenomas. Gsp and MEN-1 genes play a role in the initiation event, while p53. ras. Rb and nm23 gene s play some role in the progression of the tumor. Gsp gene. that may play a n important role in 40% of GH-producing tumor, activation of 10% of non-fun ctioning tumors and 6% of corticotroph adenomas. produces cAMP, which stimu lates cyclin D1 and D3 which later produce cdk2 and cdk 4 respectively. and stimulates cell progression from G1 to S phase, cAMP also induces ras gene , which inhibits binding of pRb with E2F that is necessary to prevent actio n of E2F in accelerating cell cycle. MEN-1 gene, although found in some spo radic tumors, is more likely associated with familial adenoma. p53, Ras, Rb , nm23 and c-myc genes play some role in the promotion of tumors especially toward their aggressive variant. p53 gene, which is found in up to 60% of ACTH producing adenomas, through action of p21 inhibits progression of cell cycle from G1 to S phase, by inhibiting the action of cyclin D3 on cdk 4 P as oncogene, in cooperation with c-myc gene, prevents the binding of pRb wi th E2F, which is necessary for preventing progression cell cycle, resulting in progression of cell cycle from G1 to S phase. Nm23 gene inhibits the ac tion of cyclin B and arrests the cell in G2 phase. Further studies will nor only be helpful in understanding the genetic pathogenesis and prognosis of pituitary tumors, but also in developing a novel treatment for patients wi th pituitary adenomas.