p21 ^Cip1 restrains pituitary tumor growth

Downregulation of miR-410 targeting the cyclin B1 gene plays a role in pituitary gonadotroph tumors

“…On the other hand previous studies have evidenced a role of the decrease in p21 (CIP1) levels in pituitary tumorigenesis, since it has been reported that p21 is able to restrain pituitary tumor growth also activating senescence program. 23 Among the downregulated miRNAs we focused our attention on the miR-410 that was one of the most downregulated miRNAs. Interestingly, it results upregulated in almost all prolactinomas and in half of the all GH-secreting adenomas analyzed, suggesting that the downregulation of miR-410 is specific of gonadotroph adenomas.…”

Programmed cell senescence: role of IL-6 in the pituitary

“…The activation of cell-cycle arrest machinery and the involvement of PTTG (Chesnokova et al 2007(Chesnokova et al , 2008 was also found in pituitary adenomas and more interestingly, a differential lineage-specific pathway restricting and controlling pituitary cell-cycle progression and triggering senescence was described (Chesnokova et al 2011). PTTG exhibits oncogene properties (Pei & Melmed 1997, Zhang et al 1999) and its expression results in the activation of DNA-damage signaling pathways, aneuploidy and chromosomal instability in vitro and in vivo (Kim et al 2005, 2007, Vlotides et al 2007, ending in pituitaryspecific senescent features (Chesnokova et al 2005(Chesnokova et al , 2007.…”

“…PTTG exhibits oncogene properties (Pei & Melmed 1997, Zhang et al 1999) and its expression results in the activation of DNA-damage signaling pathways, aneuploidy and chromosomal instability in vitro and in vivo (Kim et al 2005, 2007, Vlotides et al 2007, ending in pituitaryspecific senescent features (Chesnokova et al 2005(Chesnokova et al , 2007. Different from most human GH-producing pituitary adenomas in which PTTG overexpression is associated with p21-dependent senescence (Chesnokova et al 2008), tumors arising from the gonadotroph lineage also exhibit high PTTG levels, but p21 is not expressed in gonadotrophderived nonfunctioning pituitary adenomas, which express p15 INK4b and p16 INK4a . This could be explained by A recent work (Zhang et al 2015) has shown that the expression of IL-6 was significantly increased in aging pituitary tissues, i.e.…”

Direct promoter induction of p19Arf by Pit-1 explains the dependence receptor RET/Pit-1/p53-induced apoptosis in the pituitary somatotroph cells

“…Intrinsic senescence of the pituitary secretory cells regulated by the oncogene PTTG was proposed to explain the lack of malignant evolution of the pituitary adenomas. Again, PTTG-dependent senescence pathway seems to affect specially to somatotroph adenomas (Chesnokova et al, 2008b).…”