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.

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 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.

scholarly journals Brusatol Inhibits Tumor Growth and Increases the Efficacy of Cabergoline against Pituitary Adenomas

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zerui Wu ◽  
Yunqiu Xu ◽  
Jiadong Xu ◽  
Jianglong Lu ◽  
Lin Cai ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Pituitary Adenomas ◽  
Pituitary Tumor ◽  
Antitumor Effects ◽  
Human Pituitary ◽  
First Choice ◽  
Mtorc1 Signaling

Cabergoline (CAB) is the first choice for treatment of prolactinoma and the most common subtype of pituitary adenoma. However, drug resistance and lack of effectiveness in other pituitary tumor types remain clinical challenges to this treatment. Brusatol (BT) is known to inhibit cell growth and promote apoptosis in a variety of cancer cells. In our present studies, we investigate the effects of BT on pituitary tumor cell proliferation in vitro and in vivo. BT treatment resulted in an increase in Annexin V-expressing cells and promoted the expression of apoptosis-related proteins in rat and human pituitary tumor cells. Investigation of the mechanism underlying this effect revealed that BT increased the production of reactive oxygen species (ROS) and inhibited the phosphorylation of 4EBP1 and S6K1. Furthermore, treatment with a combination of BT and CAB resulted in greater antitumor effects than either treatment alone in nude mice and pituitary tumor cells. Collectively, our results suggest that the BT-induced ROS accumulation and inhibition of mTORC1 signaling pathway leads to inhibition of tumor growth. Combined use of CAB and BT may increase the clinical effectiveness of treatment for human pituitary adenomas.

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

MicroRNA-524-5p Functions as a Tumor Suppressor in a Human Pituitary Tumor-Derived Cell Line

2017 ◽  
Vol 49 (07) ◽  
pp. 550-557 ◽  
Author(s):  
Wang Zhen ◽  
Du Qiu ◽  
Chen Zhiyong ◽  
Wang Xin ◽  
Jian Mengyao ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Pituitary Tumor ◽  
Critical Role ◽  
Xenograft Model ◽  
Biological Properties ◽  
Migration And Invasion ◽  
Human Pituitary ◽  
Mouse Xenograft Model

AbstractClinical nonfunctional pituitary adenomas (NFAs) account for about 40% of pituitary adenomas with almost no clinically relevant hormonal symptoms. Increasing evidence shows that many microRNAs are involved in the development and progression of pituitary adenomas. MicroRNA-524-5p (miR-524-5p) has been reported to cause characteristic alterations in various tumors. However, the functional importance of miR-524-5p in NFAs remains unknown. The aim of this study was to explore the effects of overexpressing miR-524-5p on the proliferation, migration, invasion, and tumorigenicity of pituitary-derived folliculostellate (PDFS) cells using lentiviral transfection. Interestingly, the results showed that overexpressing miR-524-5p downregulated pituitary tumor-transforming gene 1 (PTTG1) binding factor (PBF) expression at both mRNA and protein levels and significantly attenuated cell proliferation, clonogenicity, migration, and invasion in vitro. Moreover, enhancing miR-524-5p blocked tumor growth in a nude mouse xenograft model in vivo. These findings suggest that miR-524-5p appears to play a critical role in the regulation of biological properties of PDFS cells, and may represent a potential therapeutic target for NFAs.

Effects of TGFβ1 on gene expression in the HP75 human pituitary tumor cell line identified by gene expression profiling

Endocrine ◽  
2008 ◽  
Vol 33 (1) ◽  
pp. 62-76 ◽  
Author(s):  
Katharina H. Ruebel ◽  
Alexey A. Leontovich ◽  
Yoshinori Tanizaki ◽  
Long Jin ◽  
Gail A. Stilling ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Cell ◽  
Gene Expression Profiling ◽  
Cell Line ◽  
Expression Profiling ◽  
Pituitary Tumor ◽  
Tumor Cell Line ◽  
Human Pituitary ◽  
Human Pituitary Tumor ◽  
Pituitary Tumor Cell

Activation of the heat shock transcription factor by hypoxia in normal and tumor cell lines in vivo and in vitro

1992 ◽  
Vol 23 (4) ◽  
pp. 891-897 ◽  
Author(s):  
Amato J. Giaccia ◽  
Elizabeth A. Auger ◽  
Albert Koong ◽  
David J. Terris ◽  
Andrew I. Minchinton ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Tumor Cell ◽  
Cell Lines ◽  
Heat Shock Transcription Factor ◽  
Tumor Cell Lines

scholarly journals Overexpressed Pituitary Tumor-Transforming Gene Causes Aneuploidy in Live Human Cells

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4991-4998 ◽  
Author(s):  
Run Yu ◽  
Wenge Lu ◽  
Jiandong Chen ◽  
Chris J. McCabe ◽  
Shlomo Melmed
Keyword(s):  
Cancer Cells ◽  
Chromosome Segregation ◽  
Pituitary Tumor ◽  
Fluorescent Protein ◽  
Human Cancer ◽  
Live Cells ◽  
Pituitary Tumor Transforming Gene ◽  
Transforming Gene

Abstract The mammalian securin, pituitary tumor-transforming gene (PTTG), is overexpressed in several tumors and transforms cells in vitro and in vivo. To test the hypothesis that PTTG overexpression causes aneuploidy, enhanced green fluorescent protein (EGFP)-tagged PTTG (PTTG-EGFP) was expressed in human H1299 cancer cells (with undetectable endogenous PTTG expression) and mitosis of individual live cells observed. Untransfected cells and cells expressing EGFP alone exhibited appropriate mitosis. PTTG-EGFP markedly prolonged prophase and metaphase, indicating that PTTG blocks progression of mitosis to anaphase. In cells that underwent apparently normal mitosis (35 of 65 cells), PTTG-EGFP was degraded about 1 min before anaphase onset. Cells that failed to degrade PTTG-EGFP exhibited asymmetrical cytokinesis without chromosome segregation (18 of 65 cells) or chromosome decondensation without cytokinesis (9 of 65 cells), resulting in appearance of a macronucleus. Fifty-one of 55 cells expressing a nondegradable mutant PTTG exhibited asymmetrical cytokinesis without chromosome segregation, and some (4 of 55) decondensed chromosomes, both resulting in macronuclear formation. During this abnormal cytokinesis, all chromosomes and spindles and both centrosomes moved to one daughter cell, suggesting potential chaos in the subsequent mitosis. In conclusion, failure of PTTG degradation or enhanced PTTG accumulation, as a consequence of overexpression, inhibits mitosis progression and chromosome segregation but does not directly affect cytokinesis, resulting in aneuploidy. These results demonstrate that PTTG induces aneuploidy in single, live, human cancer cells.

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