Abstract
Pituitary tumors are in most cases monoclonal adenomas arising from the adenohypophysial cells, and represent about 15% of intracranial tumors. They, while benign tumors, show a significant morbidity related to the endocrinological symptoms of hypo-or hyper-secretion of hormones and/or mass effect of the tumor on adjacent brain structures. Despite their considerable social impact, yet relatively little is known about the molecular events underlying pituitary tumorigenesis. Recent studies have demonstrated that the High Mobility Group A (HMGA) gene family, including HMGA1 and HMGA2, has a critical role in the development of pituitary adenomas. Indeed, the HMGA2 gene is amplified and overexpressed in several pituitary adenomas, and, consistently, transgenic mice overexpressing either Hmga1 or Hmga2 develop pituitary adenomas. The overxpression of the HMGA proteins would induce pituitary adenomas mainly by enhancing the activity of the transcription factor E2F1 and by upregulating the expression of cyclin B2 and other genes involved in the regulation of the cell cycle.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Asa SL, Ezzat S (2009) The pathogenesis of pituitary tumors. Annu Rev Pathol 4:97–126
Baldassarre G, Fedele M, Battista S, Vecchione A, Klein-Szanto AJ, Santoro M, Waldmann TA, Azimi N, Croce CM, Fusco A (2001) Onset of natural killer cell lymphomas in transgenic mice carrying a truncated HMGI-C gene by the chronic stimulation of the IL-2 and IL-15 pathway. Proc Natl Acad Sci U S A 98:7970–7975
Bettio D, Rizzi N, Giardino D, Persani L, Pecori-Giraldi F, Losa M, Larizza L (1997) Cytogenetic study of pituitary adenomas. Cancer Genet Cytogenet 98:131–136
Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC (2005) miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol 204:280–285
Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A (2006) High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 91:4769–4775
de Almeida JP, Sherman JH, Salvatori R, Quiñones-Hinojosa A (2010) Pituitary stem cells: review of the literature and current understanding. Neurosurgery 67:770–780
De Martino I, Visone R, Palmieri D, Cappabianca P, Chieffi P, Forzati F, Barbieri A, Kruhoffer M, Lombardi G, Fusco A, Fedele M (2007) The Mia/Cd-rap gene expression is downregulated by the high-mobility group a proteins in mouse pituitary adenomas. Endocr Relat Cancer 14:875–886
De Martino I, Visone R, Wierinckx A, Palmieri D, Ferraro A, Cappabianca P, Chiappetta G, Forzati F, Lombardi G, Colao A, Trouillas J, Fedele M, Fusco A (2009) HMGA proteins up-regulate CCNB2 gene in mouse and human pituitary adenomas. Cancer Res 69:1844–1850
Evans CO, Moreno CS, Zhan X, McCabe MT, Vertino PM, Desiderio DM, Oyesiku NM (2008) Molecular pathogenesis of human prolactinomas identified by gene expression profiling, RT-qPCR, and proteomic analyses. Pituitary 11:231–245
Farrell WE, Clayton RN (2003) Epigenetic change in pituitary tumorigenesis. Endocr Relat Cancer 10:323–330
Fedele M, Fusco A (2010) Role of the high mobility group A proteins in the regulation of pituitary cell cycle. J Mol Endocrinol 44:309–318
Fedele M, Battista S, Kenyon L, Baldassarre G, Fidanza V, Klein-Szanto AJ, Parlow AF, Visone R, Pierantoni GM, Outwater E, Santoro M, Croce CM, Fusco A (2002) Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas. Oncogene 21:3190–3198
Fedele M, Pentimalli F, Baldassarre G, Battista S, Klein-Szanto AJ, Kenyon L, Visone R, De Martino I, Ciarmiello A, Arra C, Viglietto G, Croce CM, Fusco A (2005) Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell lymphomas. Oncogene 24:3427–3435
Fedele M, Visone R, De Martino I, Troncone G, Palmieri D, Battista S, Ciarmiello A, Pallante P, Arra C, Melillo RM, Helin K, Croce CM, Fusco A (2006) HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity. Cancer Cell 9:459–471
Fedele M, Palmieri D, Fusco A (2010) HMGA2: a pituitary tumour subtype-specific oncogene? Mol Cell Endocrinol 326:19–24
Finelli P, Pierantoni GM, Giardino D, Losa M, Rodeschini O, Fedele M, Valtorta E, Mortini P, Croce CM, Larizza L, Fusco A (2002) The high mobility group A2 gene is amplified and overexpressed in human prolactinomas. Cancer Res 62:2398–2405
Fusco A, Fedele M (2007) Roles of HMGA proteins in cancer. Nat Rev Cancer 7:899–910
Heaney AP, Melmed S (2004) Molecular targets in pituitary tumours. Nat Rev Cancer 4:285–295
Hock R, Furusawa T, Ueda T, Bustin M (2007) HMG chromosomal proteins in development and disease. Trends Cell Biol 17:72–79
Kaddar T, Rouault JP, Chien WW, Chebel A, Gadoux M, Salles G, Ffrench M, Magaud JP (2009) Two new miR-16 targets: caprin-1 and HMGA1, proteins implicated in cell proliferation. Biol Cell 101:511–524
Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L (1989) GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature 340:692–696
Malumbres M, Barbacid M (2001) To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 1:222–231
Mayr C, Hemmann MT, Bartel DP (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315:1576–1579
Nishino J, Kim I, Chada K, Morrison SJ (2008) Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf expression. Cell 135:227–239
Pierantoni GM, Finelli P, Valtorta E, Giardino D, Rodeschini O, Esposito F, Losa M, Fusco A, Larizza L (2005) High-mobility group A2 gene expression is frequently induced in non-functioning pituitary adenomas (NFPAs), even in the absence of chromosome 12 polysomy. Endocr Relat Cancer 12:867–874
Qian ZR, Asa SL, Siomi H, Siomi MC, Yoshimoto K, Yamada S, Wang EL, Rahman MM, Inoue H, Itakura M, Kudo E, Sano T (2009) Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas. Mod Pathol 22:431–441
Wierinckx A, Auger C, Devauchelle P, Reynaud A, Chevallier P, Jan M, Perrin G, Fèvre-Montange M, Rey C, Figarella-Branger D, Raverot G, Belin MF, Lachuer J, Trouillas J (2007) A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors. Endocr Relat Cancer 14:887–900
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Fedele, M., Fusco, A. (2013). Pituitary Adenoma: Role of HMGA Proteins. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 10. Tumors of the Central Nervous System, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5681-6_18
Download citation
DOI: https://doi.org/10.1007/978-94-007-5681-6_18
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-5680-9
Online ISBN: 978-94-007-5681-6
eBook Packages: MedicineMedicine (R0)