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HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity
Monica Fedele1, Rosa Visone, Ivana De Martino
1Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, 80131 Naples, Italy.
Cancer Cell
|June 13, 2006
Summary
High mobility group AT-hook 2 (HMGA2) gene amplification drives pituitary tumor development by activating the pRB/E2F1 pathway. Suppressing E2F1 function halts tumor growth in mice, implicating this pathway in human prolactinomas.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- High mobility group AT-hook 2 (HMGA2) gene amplification and overexpression are observed in human prolactinomas.
- HMGA2 plays a critical role in pituitary tumorigenesis, as evidenced by tumor development in HMGA2 transgenic mice.
Purpose of the Study:
- To investigate the mechanism by which HMGA2 contributes to pituitary tumorigenesis.
- To explore the involvement of the pRB/E2F1 pathway in HMGA2-mediated tumor development.
Main Methods:
- Investigated the interaction between HMGA2 and pRB (retinoblastoma protein).
- Assessed E2F1 activity and acetylation in mouse pituitary adenomas.
- Utilized HMGA2 transgenic mice and E2F1 knockout mice (E2F1(-/-)) to study tumor suppression.
Main Results:
- HMGA2 interacts with pRB, displacing HDAC1 (histone deacetylase 1) from the pRB/E2F1 complex.
- This displacement leads to E2F1 acetylation and increased E2F1 activity.
- Loss of E2F1 function suppressed pituitary tumorigenesis in HMGA2 transgenic mice.
Conclusions:
- HMGA2-mediated activation of E2F1 is a crucial event in the initiation of pituitary tumors in mice.
- This mechanism is likely relevant to the development of human prolactinomas.