Abstract
Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.
Keywords: PTTG, pituitary adenoma, tumorigenesis, invasiveness, angiogenesis, senescence.
Graphical Abstract
[http://dx.doi.org/doi.org/10.1159/000192443] [PMID: 19407503]
[http://dx.doi.org/10.1159/000345673] [PMID: 23652674]
[http://dx.doi.org/10.1530/EJE-12-0763] [PMID: 23321498]
[http://dx.doi.org/10.1055/s-0029-1215588] [PMID: 19472104]
[http://dx.doi.org/10.1016/j.ecl.2014.11.003] [PMID: 25732643]
[http://dx.doi.org/10.1677/erc.1.01131] [PMID: 16954426]
[http://dx.doi.org/10.1677/erc.0.0100323] [PMID: 12790793]
[http://dx.doi.org/10.1210/jc.2004-2231] [PMID: 15741248]
[http://dx.doi.org/10.1038/ncpendmet0159] [PMID: 16932287]
[http://dx.doi.org/10.1016/j.mce.2010.02.012] [PMID: 20153804]
[http://dx.doi.org/10.1016/S0091-30220300012-8] [PMID: 12763000]
[http://dx.doi.org/10.3171/jns.2002.96.2.0195] [PMID: 11838791]
[http://dx.doi.org/10.2353/ajpath.2007.060736] [PMID: 17200207]
[PMID: 26097538]
[http://dx.doi.org/10.1007/s11102-013-0492-2] [PMID: 23720159]
[http://dx.doi.org/10.4103/0028-3886.15073] [PMID: 15805667]
[http://dx.doi.org/10.1210/jcem.84.2.5432] [PMID: 10022450]
[http://dx.doi.org/10.1677/ERC-08-0012] [PMID: 18753362]
[http://dx.doi.org/10.3171/jns.1993.78.5.0753] [PMID: 8096873]
[http://dx.doi.org/10.1677/erc.0.0090103] [PMID: 12121834]
[http://dx.doi.org/10.1177/030089160308900112] [PMID: 12729363]
[http://dx.doi.org/10.1046/j.1365-2265.2003.01598.x] [PMID: 12580928]
[http://dx.doi.org/10.1007/BF02738884] [PMID: 12114703]
[http://dx.doi.org/10.3121/cmr.4.2.130] [PMID: 16809406]
[http://dx.doi.org/10.1210/me.2005-0137] [PMID: 15919720]
[http://dx.doi.org/10.1016/j.acthis.2013.09.011] [PMID: 24176776]
[http://dx.doi.org/10.1210/er.2006-0042] [PMID: 17325339]
[http://dx.doi.org/10.1210/mend.11.4.9911] [PMID: 9092795]
[http://dx.doi.org/10.1007/s10528-015-9709-6] [PMID: 26718581]
[http://dx.doi.org/10.1172/JCI20401] [PMID: 14660734]
[http://dx.doi.org/10.1046/j.1365-2265.2003.01687.x] [PMID: 12780741]
[http://dx.doi.org/10.1210/mend.14.8.0501] [PMID: 10935539]
[http://dx.doi.org/10.1093/emboj/20.4.792] [PMID: 11179223]
[http://dx.doi.org/10.1210/jcem.86.2.7184] [PMID: 11158059]
[http://dx.doi.org/10.1210/mend.13.1.0225] [PMID: 9892021]
[http://dx.doi.org/10.1093/nar/29.6.1300] [PMID: 11238996]
[http://dx.doi.org/10.1210/jc.2002-020309] [PMID: 12213878]
[http://dx.doi.org/10.1074/jbc.M002451200] [PMID: 10906323]
[http://dx.doi.org/10.1155/2010/472067] [PMID: 20978326]
[http://dx.doi.org/10.7314/APJCP.2013.14.11.6245] [PMID: 24377512]
[http://dx.doi.org/10.1111/j.1365-2265.2006.02630.x] [PMID: 16984249]
[http://dx.doi.org/10.1210/me.2004-0403] [PMID: 15677710]
[http://dx.doi.org/10.3892/ijo.31.1.137] [PMID: 17549414]
[http://dx.doi.org/10.1002/hep.21137] [PMID: 16628636]
[http://dx.doi.org/10.1007/s13277-013-0686-2] [PMID: 23404407]
[http://dx.doi.org/10.1530/eje.0.1480203] [PMID: 12590639]
[http://dx.doi.org/10.1677/ERC-07-0062] [PMID: 17914117]
[http://dx.doi.org/10.1210/jc.2009-1191] [PMID: 20164287]
[http://dx.doi.org/10.1677/jme.1.01606] [PMID: 15591026]
[http://dx.doi.org/10.1091/mbc.6.2.185] [PMID: 7787245]
[http://dx.doi.org/10.1006/geno.1998.5217] [PMID: 9570958]
[http://dx.doi.org/10.1038/sj.onc.1210221] [PMID: 17297475]
[http://dx.doi.org/10.1242/jcs.045427] [PMID: 19706688]
[http://dx.doi.org/10.1210/en.2011-2030] [PMID: 22535767]
[http://dx.doi.org/10.1111/cen.12007] [PMID: 22888961]
[PMID: 22522436]
[http://dx.doi.org/10.1074/jbc.M910105199] [PMID: 10781616]
[http://dx.doi.org/10.1038/15275] [PMID: 10546001]
[http://dx.doi.org/10.1385/EP:17:2:143] [PMID: 17159247]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-0720] [PMID: 21844185]
[http://dx.doi.org/10.1038/onc.2017.154] [PMID: 28504713]
[http://dx.doi.org/10.1210/en.2012-2156] [PMID: 23867215]
[http://dx.doi.org/10.4149/gpb_2016035] [PMID: 27787230]
[http://dx.doi.org/10.1677/joe.0.1620163] [PMID: 10425453]
[http://dx.doi.org/10.1038/sj.onc.1203320] [PMID: 10656688]
[http://dx.doi.org/10.1017/S1462399410001699] [PMID: 21129230]
[http://dx.doi.org/10.1038/sj.cdd.4402254] [PMID: 17962814]
[http://dx.doi.org/10.1126/science.285.5426.418] [PMID: 10411507]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0974] [PMID: 17975001]
[http://dx.doi.org/10.1038/sj.onc.1208659] [PMID: 15897900]
[http://dx.doi.org/10.1093/carcin/bgl202] [PMID: 17071631]
[http://dx.doi.org/10.1210/en.2003-0305] [PMID: 12960092]
[http://dx.doi.org/10.1159/000079044] [PMID: 15281346]
[http://dx.doi.org/10.1126/science.1140735] [PMID: 18323444]
[PMID: 16447816]
[http://dx.doi.org/10.1038/nrm2858] [PMID: 20177397]
[http://dx.doi.org/10.1210/mend.15.11.0729] [PMID: 11682618]
[http://dx.doi.org/10.1016/S0092-86740100340-3] [PMID: 11371342]
[http://dx.doi.org/10.1093/carcin/bgp268] [PMID: 19887512]
[http://dx.doi.org/10.1080/08977190802001389] [PMID: 18365874]
[http://dx.doi.org/10.2174/156652408785747988] [PMID: 18781952]
[http://dx.doi.org/10.1186/1476-4598-3-18] [PMID: 15242522]
[http://dx.doi.org/10.1002/mc.20738] [PMID: 21268135]
[http://dx.doi.org/10.1093/abbs/gmv026] [PMID: 25908389]
[http://dx.doi.org/10.18632/oncotarget.5726] [PMID: 26516926]
[http://dx.doi.org/10.1158/0008-5472.CAN-13-3555] [PMID: 24906624]
[http://dx.doi.org/10.1210/me.2009-0161] [PMID: 19837943]
[http://dx.doi.org/10.4161/cbt.3.12.1494] [PMID: 15662116]
[http://dx.doi.org/10.1210/me.2010-0091] [PMID: 20660298]
[http://dx.doi.org/10.1038/nrc883] [PMID: 12209154]
[http://dx.doi.org/10.1101/gad.13.12.1501] [PMID: 10385618]
[http://dx.doi.org/10.1073/pnas.1018091108] [PMID: 21536883]
[http://dx.doi.org/10.1073/pnas.96.8.4240] [PMID: 10200246]
[http://dx.doi.org/10.1126/science.296.5573.1655] [PMID: 12040186]
[http://dx.doi.org/10.1074/jbc.273.22.13375] [PMID: 9593664]
[http://dx.doi.org/10.1016/S0002-94401065040-7] [PMID: 10793080]
[http://dx.doi.org/10.1016/j.anndiagpath.2008.02.001] [PMID: 18620995]
[http://dx.doi.org/10.1158/0008-5472.CAN-09-3531] [PMID: 20406982]
[http://dx.doi.org/10.1074/jbc.275.11.7459] [PMID: 10713046]
[http://dx.doi.org/10.1096/fj.02-0948com] [PMID: 12958169]
[http://dx.doi.org/10.1038/sj.onc.1202140] [PMID: 9811450]
[http://dx.doi.org/10.1007/s12013-017-0810-9] [PMID: 28646413]
[http://dx.doi.org/10.1530/JOE-11-0064] [PMID: 21450804]
[http://dx.doi.org/10.1210/me.2006-0280] [PMID: 16959877]
[http://dx.doi.org/10.1023/A:1009998207652] [PMID: 11081205]
[PMID: 21422801]
[PMID: 10649822]
[http://dx.doi.org/10.1001/jama.1983.03330400050024] [PMID: 6834618]
[http://dx.doi.org/10.1016/0304-38359490214-3] [PMID: 7812932]
[http://dx.doi.org/10.1186/1476-4598-6-4] [PMID: 17222350]
[http://dx.doi.org/10.1007/s11060-010-0326-2] [PMID: 20700755]
[http://dx.doi.org/10.1210/me.2013-1245] [PMID: 24284820]
[http://dx.doi.org/10.1385/ENDO:11:3:217] [PMID: 10786818]
[PMID: 8308015]
[http://dx.doi.org/10.1210/jc.2010-3040] [PMID: 21632819]
[http://dx.doi.org/10.1172/JCI0214264] [PMID: 11805140]
[http://dx.doi.org/10.1007/s11060-013-1351-8] [PMID: 24407733]
[PMID: 8232319]
[http://dx.doi.org/10.1210/me.2001-0006] [PMID: 12554778]
[PMID: 27830003]
[http://dx.doi.org/10.1289/ehp.7505] [PMID: 15811834]
[http://dx.doi.org/10.1007/s12264-014-1510-8] [PMID: 25754146]
[http://dx.doi.org/10.1016/j.yfrne.2014.08.005] [PMID: 25223867]
[http://dx.doi.org/10.1007/s12020-015-0802-8] [PMID: 26578364]
[http://dx.doi.org/10.1007/s12020-014-0445-1] [PMID: 25300784]
[PMID: 8501143]
[http://dx.doi.org/10.1210/jc.2010-0476] [PMID: 20444909]
[http://dx.doi.org/10.1016/S0960-07600100032-2] [PMID: 11358670]
[http://dx.doi.org/10.1016/0014-57939480452-4] [PMID: 8137936]
[http://dx.doi.org/10.1089/ars.2008.2153] [PMID: 18834328]
[http://dx.doi.org/10.1095/biolreprod64.2.625] [PMID: 11159366]
[http://dx.doi.org/10.1096/fj.06-6121fje] [PMID: 17065216]
[http://dx.doi.org/10.1210/endo.141.4.7419] [PMID: 10746660]
[http://dx.doi.org/10.1002/(SICI)1097-00291997101539:2<138:AID-JEMT5>3.0.CO;2-H] [PMID: 9361265]
[http://dx.doi.org/10.1179/1743132814Y.0000000419] [PMID: 25023895]
[http://dx.doi.org/10.1055/s-2004-815722] [PMID: 14758567]
[http://dx.doi.org/10.1210/en.2008-1625] [PMID: 19359387]
[http://dx.doi.org/10.1210/jcem.76.5.8098714] [PMID: 8098714]
[http://dx.doi.org/10.1210/jcem.75.6.1464644] [PMID: 1464644]
[http://dx.doi.org/10.1210/jcem.80.3.7883846] [PMID: 7883846]
[http://dx.doi.org/10.1074/jbc.M009654200] [PMID: 11115508]
[http://dx.doi.org/10.1155/2014/608497] [PMID: 25505910]
[http://dx.doi.org/10.1016/j.mce.2007.08.006] [PMID: 17928133]
[http://dx.doi.org/10.1016/j.jbiotec.2008.09.004] [PMID: 18977400]
[http://dx.doi.org/10.5137/1019-5149.JTN.20760-17.1] [PMID: 29091246]
[http://dx.doi.org/10.1056/NEJM197111182852108] [PMID: 4938153]
[http://dx.doi.org/10.1210/jcem-67-4-713] [PMID: 3417848]
[http://dx.doi.org/10.3892/ijo.16.2.253] [PMID: 10639567]
[http://dx.doi.org/10.1385/EP:16:2:115] [PMID: 16199896]
[http://dx.doi.org/10.1093/jnci/djj232] [PMID: 16788159]
[PMID: 21965758]
[http://dx.doi.org/10.1007/s12022-010-9119-6] [PMID: 20473646]
[http://dx.doi.org/10.1093/carcin/bgl231] [PMID: 17127711]
[http://dx.doi.org/10.1016/j.bbrc.2005.03.124] [PMID: 15845362]
[http://dx.doi.org/10.1016/j.ejca.2007.05.021] [PMID: 17624760]
[http://dx.doi.org/10.1016/j.endonu.2012.09.005] [PMID: 23416216]
[PMID: 14710361]
[http://dx.doi.org/10.1128/MCB.14.7.4588] [PMID: 8007963]
[http://dx.doi.org/10.1016/S1055-32071830066-8] [PMID: 11382588]
[http://dx.doi.org/10.1016/j.ejca.2005.08.006] [PMID: 16209919]
[http://dx.doi.org/10.1038/sj.onc.1205211] [PMID: 11896576]
[http://dx.doi.org/10.1210/en.2002-0149] [PMID: 12746293]
[http://dx.doi.org/10.1016/j.gene.2003.08.012] [PMID: 14644503]
[http://dx.doi.org/10.1038/sj.onc.1210339] [PMID: 17353909]
[http://dx.doi.org/10.1074/jbc.M201753200] [PMID: 11904305]
[http://dx.doi.org/10.1091/mbc.e04-05-0374] [PMID: 15342781]
[http://dx.doi.org/10.1111/j.1749-6632.2009.04911.x] [PMID: 19723038]
[http://dx.doi.org/10.1038/onc.2013.16] [PMID: 23416975]
[http://dx.doi.org/10.1172/JCI78173] [PMID: 25774503]
[http://dx.doi.org/10.1210/en.2008-0972] [PMID: 19213844]
[http://dx.doi.org/10.1038/326515a0] [PMID: 2882423]
[PMID: 16584090]
[http://dx.doi.org/10.1007/978-3-642-72149-6_4] [PMID: 9928526]
[http://dx.doi.org/10.1016/j.humpath.2009.10.023] [PMID: 20381119]
[http://dx.doi.org/10.1530/JME-12-0113] [PMID: 22822048]
[http://dx.doi.org/10.1007/s11102-017-0803-0] [PMID: 28342098]
[http://dx.doi.org/10.1210/jc.2009-0471] [PMID: 19820025]
[http://dx.doi.org/10.3390/jcm5040043] [PMID: 27058562]
[http://dx.doi.org/10.1242/dev.105445] [PMID: 25564621]
[http://dx.doi.org/10.1038/ncb434] [PMID: 17762890]
[PMID: 25964539]
[http://dx.doi.org/10.1016/j.canlet.2011.06.033] [PMID: 21839581]
[http://dx.doi.org/10.1016/j.lfs.2015.04.010] [PMID: 25936962]
[http://dx.doi.org/10.1007/s11033-009-9502-x] [PMID: 19288218]
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3401] [PMID: 16585154]
[http://dx.doi.org/10.1038/nrm1835] [PMID: 16493418]
[http://dx.doi.org/10.1038/onc.2011.488] [PMID: 22081074]
[http://dx.doi.org/10.1007/s11010-010-0396-7] [PMID: 20177740]
[PMID: 27186413]
[http://dx.doi.org/10.1016/j.canlet.2008.11.010] [PMID: 19097686]
[PMID: 11280798]
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0610] [PMID: 15161697]
[http://dx.doi.org/10.1038/onc.2011.149] [PMID: 21532623]
[http://dx.doi.org/10.1016/j.clinimag.2010.06.002] [PMID: 21513851]
[http://dx.doi.org/10.1042/bse0380021] [PMID: 12463159]
[http://dx.doi.org/10.3390/molecules191016588] [PMID: 25322282]
[http://dx.doi.org/10.3892/ijo.2014.2685] [PMID: 25270791]
[http://dx.doi.org/10.1067/mhn.2003.8] [PMID: 12574771]
[http://dx.doi.org/10.1016/j.cell.2010.03.015] [PMID: 20371345]
[http://dx.doi.org/10.1073/pnas.97.8.3884] [PMID: 10760260]
[http://dx.doi.org/10.1038/sj.cgt.7700642] [PMID: 14605668]
[http://dx.doi.org/10.2152/jmi.52.151] [PMID: 16167532]
[http://dx.doi.org/10.1186/1476-4598-5-61] [PMID: 17096843]
[http://dx.doi.org/10.1177/0363546512473817] [PMID: 23404084]
[http://dx.doi.org/10.1038/370061a0] [PMID: 8015608]
[http://dx.doi.org/10.1038/nrm2125] [PMID: 17318226]
[http://dx.doi.org/10.1146/annurev.cellbio.24.110707.175315] [PMID: 19575644]
[http://dx.doi.org/10.1371/journal.pcbi.1003086] [PMID: 23737743]
[http://dx.doi.org/10.1016/j.yexcr.2016.10.007] [PMID: 27737732]
[http://dx.doi.org/10.1097/MED.0b013e328354b2e2] [PMID: 22617628]
[http://dx.doi.org/10.1126/science.1116801] [PMID: 16081723]
[http://dx.doi.org/10.1038/436642a] [PMID: 16079833]
[http://dx.doi.org/10.1016/j.cell.2007.07.003] [PMID: 17662938]
[http://dx.doi.org/10.1056/NEJMra062285] [PMID: 16957149]
[http://dx.doi.org/10.1016/j.cell.2008.05.027] [PMID: 18555773]
[http://dx.doi.org/10.1038/nature03890] [PMID: 16079850]
[http://dx.doi.org/10.1038/nature03841] [PMID: 16079837]
[http://dx.doi.org/10.1371/journal.pone.0017924] [PMID: 21464964]
[http://dx.doi.org/10.1172/JCI20761] [PMID: 14722605]
[http://dx.doi.org/10.1242/jcs.03293] [PMID: 17158908]
[http://dx.doi.org/10.1186/1471-2407-12-532] [PMID: 23164239]
[http://dx.doi.org/10.1038/ng997] [PMID: 12355087]
[http://dx.doi.org/10.18632/oncotarget.5003] [PMID: 26320179]
[http://dx.doi.org/10.1074/jbc.M203793200] [PMID: 12403781]
[http://dx.doi.org/10.1074/jbc.M311912200] [PMID: 15016801]
[http://dx.doi.org/10.1073/pnas.0606343104] [PMID: 17170138]
[http://dx.doi.org/10.1073/pnas.0804810105] [PMID: 18981426]
[http://dx.doi.org/10.1038/sj.onc.1208615] [PMID: 15838523]
[http://dx.doi.org/10.1074/jbc.M109.096255] [PMID: 20452981]
[http://dx.doi.org/10.1016/S0092-86740200734-1] [PMID: 12015983]
[http://dx.doi.org/10.1146/annurev.pathol.4.110807.092259] [PMID: 19400692]
[http://dx.doi.org/10.1093/jnci/djp063] [PMID: 19401549]
[http://dx.doi.org/10.1073/pnas.86.18.7123] [PMID: 2780565]
[http://dx.doi.org/10.1161/ATVBAHA.109.190058] [PMID: 19696405]
[http://dx.doi.org/10.1067/mva.2001.116301] [PMID: 11668329]
[http://dx.doi.org/10.1073/pnas.1233633100] [PMID: 12886021]
[http://dx.doi.org/10.1016/S0065-230X(09)05007-6] [PMID: 19879426]
[http://dx.doi.org/10.1038/onc.2011.92] [PMID: 21460853]
[http://dx.doi.org/10.4161/cbt.2.4.430] [PMID: 14508108]
[http://dx.doi.org/10.1074/jbc.M412569200] [PMID: 15689620]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-2912] [PMID: 19147550]
[http://dx.doi.org/10.1042/bj20020508] [PMID: 12006103]
[http://dx.doi.org/10.1016/j.tcb.2007.07.004] [PMID: 17658261]
[http://dx.doi.org/10.1210/me.2012-1158] [PMID: 23051594]
[http://dx.doi.org/10.1016/j.cell.2009.04.037] [PMID: 19410540]
[http://dx.doi.org/10.1038/modpathol.2010.169] [PMID: 21478824]
[http://dx.doi.org/10.1210/me.2005-0303] [PMID: 16840539]
[http://dx.doi.org/10.1677/ERC-09-0140] [PMID: 19903745]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2077] [PMID: 15492264]
[http://dx.doi.org/10.1007/s11102-016-0777-3] [PMID: 27853917]
[http://dx.doi.org/10.1186/gm563] [PMID: 25690659]
[http://dx.doi.org/10.1210/en.2013-1646] [PMID: 24506068]
[http://dx.doi.org/10.1002/mc.22254] [PMID: 25408419]
[http://dx.doi.org/10.1186/1746-1596-2-20] [PMID: 17597515]
[http://dx.doi.org/10.3109/01913129109021886] [PMID: 1871899]
[http://dx.doi.org/10.1038/nrc2560] [PMID: 19132009]
[http://dx.doi.org/10.1089/gtmb.2013.0447] [PMID: 24611443]