PTTG is a Secretory Protein in Human Pituitary Adenomas and in Mouse Pituitary Tumor Cell Lines

2007 ◽  
Vol 18 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Takeo Minematsu ◽  
Noboru Egashira ◽  
Hanako Kajiya ◽  
Mao Takei ◽  
Susumu Takekoshi ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Pituitary Adenomas ◽  
Pituitary Tumor ◽  
Secretory Protein ◽  
Tumor Cell Lines ◽  
Human Pituitary ◽  
Human Pituitary Adenomas ◽  
Mouse Pituitary ◽  
Pituitary Tumor Cell

scholarly journals Pituitary Tumor Suppression by Combination of Cabergoline and Chloroquine

2017 ◽  
Vol 102 (10) ◽  
pp. 3692-3703 ◽  
Author(s):  
Shao Jian Lin ◽  
Ze Rui Wu ◽  
Lei Cao ◽  
Yong Zhang ◽  
Zhi Gen Leng ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Pituitary Adenomas ◽  
Pituitary Tumor ◽  
Human Cancer ◽  
Primary Cultures ◽  
Human Pituitary ◽  
Pituitary Tumor Cell

Abstract Context The dopamine agonist cabergoline (CAB) has been used widely in the treatment of prolactinomas and other types of pituitary adenomas, but its clinical use is hampered by intolerance in some patients with prolactinoma and lack of effectiveness in other pituitary tumor types. Chloroquine (CQ) is an old drug widely used to treat malaria. Recent studies, including our own, have revealed that CAB and CQ are involved in induction of autophagy and activation of autophagic cell death. Objective To test whether CAB and CQ can function cooperatively to suppress growth of pituitary adenomas as well as other cancers. Results In vitro studies using the rat pituitary tumor cell lines MMQ and GH3, human pituitary tumor cell primary cultures, and several human cancer cell lines showed that CQ enhanced suppression of cell proliferation by CAB. These results were confirmed in in vivo xenograft models in nude mice and estrogen-induced rat prolactinomas. To understand the mechanism of combined CAB and CQ action, we established a low-CAB-dose condition in which CAB was able to induce autophagy but failed to suppress cell growth. Addition of CQ to low-dose CAB blocked normal autophagic cycles and induced apoptosis, evidenced by the further accumulation of p62/caspase-8/LC3-II. Conclusion The data suggest that combined use of CAB and CQ may increase clinical effectiveness in treatment of human pituitary adenomas, as well as other cancers, making it an attractive option in tumor and cancer therapies.

CUL4A is overexpressed in human pituitary adenomas and regulates pituitary tumor cell proliferation

2014 ◽  
Vol 116 (3) ◽  
pp. 625-632 ◽  
Author(s):  
Yangyang Xu ◽  
Yunshan Wang ◽  
Guangxin Ma ◽  
Qin Wang ◽  
Guangwei Wei
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Pituitary Adenomas ◽  
Pituitary Tumor ◽  
Tumor Cell Proliferation ◽  
Human Pituitary ◽  
Human Pituitary Adenomas ◽  
Pituitary Tumor Cell

scholarly journals Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity

2018 ◽  
Vol 25 (6) ◽  
pp. 665-676 ◽  
Author(s):  
M Fuertes ◽  
M Sapochnik ◽  
L Tedesco ◽  
S Senin ◽  
A Attorresi ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Pituitary Adenomas ◽  
Pituitary Tumor ◽  
Mrna Level ◽  
Critical Role ◽  
Gene Promoter ◽  
Tumor Cell Line ◽  
Protein Stabilization ◽  
Human Pituitary ◽  
Pituitary Tumor Cell

Increased levels of the proto-oncogene pituitary tumor-transforming gene 1 (PTTG) have been repeatedly reported in several human solid tumors, especially in endocrine-related tumors such as pituitary adenomas. Securin PTTG has a critical role in pituitary tumorigenesis. However, the cause of upregulation has not been found yet, despite analyses made at the gene, promoter and mRNA level that show that no mutations, epigenetic modifications or other mechanisms that deregulate its expression may explain its overexpression and action as an oncogene. We describe that high PTTG protein levels are induced by the RWD-containing sumoylation enhancer (RWDD3 or RSUME), a protein originally identified in the same pituitary tumor cell line in which PTTG was also cloned. We demonstrate that PTTG and RSUME have a positive expression correlation in human pituitary adenomas. RSUME increases PTTG protein in pituitary tumor cell lines, prolongs the half-life of PTTG protein and regulates the PTTG induction by estradiol. As a consequence, RSUME enhances PTTG transcription factor and securin activities. PTTG hyperactivity on the cell cycle resulted in recurrent and unequal divisions without cytokinesis, and the consequential appearance of aneuploidies and multinucleated cells in the tumor. RSUME knockdown diminishes securin PTTG and reduces its tumorigenic potential in a xenograft mouse model. Taken together, our findings show that PTTG high protein steady state levels account for PTTG tumor abundance and demonstrate a critical role of RSUME in this process in pituitary tumor cells.

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