Role of the high mobility group A proteins in the regulation of pituitary cell cycle.
Pituitary cells are particularly sensitive to alterations of the cell cycle machinery. In fact, mutations affecting expression of proteins critical for cell cycle progression, including retinoblastoma protein, cyclins D1 and D3, p16(INK4A), and p27(kip1), are frequent in human pituitary adenomas. Similarly, both targeted disruption and overexpression of either cell cycle inhibitors or activators, respectively, lead to the development of pituitary adenomas in mice. Recent evidence has added the high mobility group A (HMGA) proteins as a new class of cell cycle regulators that play significant roles in the pathways that lead to pituitary tumor evolution in both humans and experimental animal models. Here, we first review the role of the cell cycle in pituitary tumorigenesis, as witnessed by human pathology and transgenic mice; and then, we focus on HMGA proteins and their cell cycle-related role in pituitary tumorigenesis.
Fedele
Monica
M
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, 80131 Naples, Italy. mfedele@unina.it
Fusco
Alfredo
A
D000236:Adenoma / Q000235:genetics; D000328:Adult; D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D056743:Cyclin D3 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D005260:Female; D024003:HMGA Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D010902:Pituitary Gland / Q000378:metabolism* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D018797:Cell Cycle Proteins; D056743:Cyclin D3; D019941:Cyclin-Dependent Kinase Inhibitor p16; D024003:HMGA Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27