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Biochem Genet. 2016 Apr;54(2):107-19. doi: 10.1007/s10528-015-9709-6. Epub 2015 Dec 30.

Molecular Mechanisms Underlying Pituitary Pathogenesis.

Author information

1
Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, C1425FQD, Buenos Aires, Argentina.
2
Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, C1425FQD, Buenos Aires, Argentina. earzt@ibioba-mpsp-conicet.gov.ar.
3
Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina. earzt@ibioba-mpsp-conicet.gov.ar.

Abstract

During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors.

KEYWORDS:

IL-6; OIS; PTTG; Pituitary tumors; Senescence

PMID:
26718581
DOI:
10.1007/s10528-015-9709-6
[Indexed for MEDLINE]

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