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 genes play some role in the progression of the tumor. Gsp gene, that may play an important role in 40% of GH-producing tumor, activation of 10% of non-functioning tumors and 6% of corticotroph adenomas, produces cAMP, which stimulates cyclin D1 and D3 which later produce cdk2 and cdk4 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 action of E2F in accelerating cell cycle. MEN-1 gene, although found in some sporadic 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 cdk4. Ras oncogene, in cooperation with c-myc gene, prevents the binding of pRb with E2F, which is necessary for preventing progression cell cycle, resulting in progression of cell cycle from G1 to S phase. Nm23 gene inhibits the action of cyclin B and arrests the cell in G2 phase. Further studies will not only be helpful in understanding the genetic pathogenesis and prognosis of pituitary tumors, but also in developing a novel treatment for patients with pituitary adenomas.
Suhardja
A S
AS
Division of Neurosurgery, University of Toronto, Ontario, Canada.
Kovacs
K T
KT
Rutka
J T
JT
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D018450:Disease Progression; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D009857:Oncogenes / Q000502:physiology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D011519:Proto-Oncogenes / Q000502:physiology