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Titolo:
Molecular pathogenesis of pituitary tumors
Autore:
Farrell, WE; Clayton, RN;
Indirizzi:
Keele Univ, N Staffordshire Hosp, Ctr Cell & Mol Med, Stoke On Trent ST4 7QB, Staffs, England Keele Univ Stoke On Trent Staffs England ST4 7QB ST4 7QB, Staffs, England
Titolo Testata:
FRONTIERS IN NEUROENDOCRINOLOGY
fascicolo: 3, volume: 21, anno: 2000,
pagine: 174 - 198
SICI:
0091-3022(200007)21:3<174:MPOPT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSFORMING GENE PTTG; NERVE GROWTH-FACTOR; HORMONE-RELEASING HORMONE; HUMAN ENDOCRINE TUMORS; FRAGILE-X-SYNDROME; DNA METHYLATION; SUPPRESSOR GENE; MEN1 GENE; CELL-LINES; P27(KIP1) EXPRESSION;
Keywords:
tumor suppressor gene; oncogene; CpG island; methylation;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
97
Recensione:
Indirizzi per estratti:
Indirizzo: Farrell, WE Keele Univ, N Staffordshire Hosp, Ctr Cell & Mol Med, Thornburrow Dr, Stoke On Trent ST4 7QB, Staffs, England Keele Univ Thornburrow Dr Stoke On Trent Staffs England ST4 7QB
Citazione:
W.E. Farrell e R.N. Clayton, "Molecular pathogenesis of pituitary tumors", FRONT NEURO, 21(3), 2000, pp. 174-198

Abstract

Pituitary tumors are the result of a monoclonal outgrowth. where the intrinsic genetic defects involve oncogenes, tumor suppressor genes (TSG), and most likely genes responsible for differentiation. In addition, hypothalamicand intrapituitary derived growth factors are imposed upon these aberrant cells, contributing to their growth characteristics. While histological examination will not identify those tumors likely to progress toward an invasive phenotype or those destined toward recurrence recent advances in the molecular pathology of these tumors holds significant promise for prediction of recurrence and the design of novel treatment strategies. Moreover, emerging data clearly indicate that different molecular mechanisms are involved in the pathogenesis of the various pituitary tumor subtypes. Until recently the gsp oncogene was the only oncogene significantly associated with pituitary tumors; however, emerging data have describe a role for PTTG and cyclinD1 in pituitary tumorigenesis. For known and putative TSG loci, allelic losses on the long arms of chromosomes 10, 11, and 13 are significantly associated with the transition from the noninvasive to the invasive and metastatic phenotype, while losses on chromosome 9p occur early in pituitary tumorigenesis. Studies of known TSG at these loci, including the menin gene and RBI, would suggest a limited role, if any, in pituitary tumors. However, loss of pRB is evident in a proportion of somatotropinomas but is not associated with allelic loss of an RBI intragenic marker. The gene encoding p16/CDKN2A is neither deleted nor mutated in pituitary tumors; however, its associated CPG island is frequently methylated and is associated with a loss of p16 protein expression. Allelic losses on chromosome 9p, frequent methylation, and loss of p16 protein appear as early changes in nonfunctional tumors,whereas they are infrequent events in somatotropinomas. The functional consequence of enforced expression of p16/CDKN2A in the mouse corticotroph cell line AtT20 has shown that it is responsible for a profound reduction in cell proliferation and the mechanism is a G(1) arrest, mimicking the in vivorole of this cell cycle regulator in most tissues. The combined data from several groups show that the allelic losses reported at known TSG loci are not accompanied by mutation in the retained allele. However, since abnormalmethylation patterns may precede and predispose toward genetic instabilitythis could account for the allelic losses on these chromosomes. Equally, since DNA methylation may lead to reduced expression of a gene it might alsoaccount for the reduced expression of as yet unidentified TSGs implicated in pituitary tumorigenesis. Collectively these studies hold significant promise as markers predictive of tumor behavior and point to novel treatment strategics, which may include the reactivation of TSGs that are intact but silenced through epigenetic mechanisms. (C) 2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 13:36:02