Critical role of the HMGA2 gene in pituitary adenomas.
The molecular pathway leading to pituitary tumorigenesis is still largely unknown and is one of the challenges of the endocrine oncology. The development of pituitary adenomas in HMGA2 transgenic mice and the finding of HMGA2 amplification and overexpression in human pituitary adenomas led us to investigate the mechanism by which the HMGA2 gene plays a crucial role in pituitary oncogenesis. This mechanism has been recently described by our group: it entails the acetylation of E2F1, and its consequent enhanced activity, following the displacement of HDAC1 from the pRB/E2F1 inhibitory complex. Based on the mating between HMGA2 transgenic and E2F1 knockout mice, the activation of E2F1 appears to be the main mechanism of the onset of HMGA2-induced pituitary adenoma development. Nevertheless, other events may be also involved in this process, and are discussed here.
Fedele
Monica
M
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Naples, Italy.
Pierantoni
Giovanna Maria
GM
Visone
Rosa
R
Fusco
Alfredo
A
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D025743:HMGA2 Protein / Q000235:genetics*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015533:Transcriptional Activation / Q000235:genetics
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D025743:HMGA2 Protein; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases