Differential expression of metallothionein isoforms in nasopharyngeal cancer and inhibition of cell growth by antisense down-regulation of metallothionein-2A

2005 ◽  
Author(s):  
Owen Tan ◽  
Boon-Huat Bay ◽  
Vincent Chow
Keyword(s):  
Cell Growth ◽  
Differential Expression ◽  
Nasopharyngeal Cancer ◽  
Down Regulation ◽  
Metallothionein Isoforms

Ailanthone inhibits cell growth and migration of cisplatin resistant bladder cancer cells through down-regulation of Nrf2, YAP, and c-Myc expression.

Phytomedicine ◽  
2019 ◽  
Vol 56 ◽  
pp. 156-164 ◽  
Author(s):  
Martina Daga ◽  
Stefania Pizzimenti ◽  
Chiara Dianzani ◽  
Marie Angele Cucci ◽  
Roberta Cavalli ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Down Regulation ◽  
Cell Growth And Migration ◽  
Bladder Cancer Cells ◽  
And Migration

scholarly journals LncRNA GHET1 promotes cervical cancer progression through regulating AKT/mTOR and Wnt/β-catenin signaling pathways

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Zhihui Liu ◽  
Sukun Luo ◽  
Meiqin Wu ◽  
Chong Huang ◽  
Huifen Shi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Growth ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Gynecological Cancer ◽  
Preliminary Investigation ◽  
Loss Of Function ◽  
Down Regulation ◽  
Mesenchymal Transition ◽  
Dismal Prognosis

Abstract Cervical cancer (CC) is a prevalent gynecological cancer, and the patients with CC usually suffer from dismal prognosis. Long non-coding RNAs (lncRNAs) are demonstrated to serve as promising biological targets in human cancers. Gastric carcinoma proliferation enhancing transcript 1 (GHET1) has been revealed to function as an oncogene in several cancers, but it has never been investigated in CC. We proposed to examine the biological role of GHET1 in CC and the underlying mechanism and validated the up-regulated expression of GHET1 in CC cell lines. Loss-of-function assays demonstrated that down-regulation of GHET1 inhibited cell growth, migration and epithelial-to-mesenchymal transition (EMT) in CC. Furthermore, we validated that GHET1 down-regulation could inactivate AKT/mTOR and Wnt/β-catenin pathways, and that respective activation of these two pathways abrogated the inhibitive effect of GHET1 knockdown on CC cell growth, migration and EMT. Moreover, we unfolded a preliminary investigation on the modulation of GHET1 on AKT/mTOR and Wnt/β-catenin pathways. We found that GHET1 stabilized E2F6 mRNA through interacting with IGF2BP2, so as to regulate the activity of AKT/mTOR and Wnt/β-catenin pathways. Rescue assays also proved that GHET1 regulated these two pathways and CC cell growth, migration and EMT through E2F6. In conclusion, we revealed that down-regulation of GHET1 suppresses cervical cancer progression through regulating AKT/mTOR and Wnt/β-catenin signaling pathways, indicating GHET1 as a promising molecular biomarker for CC treatment improvement.

scholarly journals The Differential Expression of Myometrial Connexin-43, Cyclooxygenase-1 and -2, and Gsα Proteins in the Upper and Lower Segments of the Human Uterus during Pregnancy and Labor1

1999 ◽  
Vol 84 (5) ◽  
pp. 1705-1710 ◽  
Author(s):  
Colette Sparey ◽  
Stephen C. Robson ◽  
Jarrod Bailey ◽  
Fiona Lyall ◽  
G. Nicholas Europe-Finner
Keyword(s):  
Gap Junction ◽  
Differential Expression ◽  
Connexin 43 ◽  
Cervical Ripening ◽  
Human Uterus ◽  
Down Regulation ◽  
Specific Antibodies ◽  
Cyclooxygenase 1 ◽  
Associated Proteins ◽  
Cox 1

There is evidence from many studies indicating that a number of specific quiescent and contractile associated proteins are temporally regulated in the myometrium during pregnancy. In this present investigation we provide data that strongly suggest that myometrial connexin-43, cyclooxygenase-1 and -2 (COX-1 and -2), and Gsα proteins are also spatially expressed within the human uterus during pregnancy and labor. Using paired lower and upper segment myometrial samples taken from individual women at term and during spontaneous labor, we have measured the expression of these proteins by immunoblotting with specific antibodies. We report that the myometrial gap junction connexin-43 protein is expressed at much greater levels in the upper uterine compared to the lower uterine segment and that this difference is even more pronounced during the course of labor. Conversely, myometrial COX-1 and -2 proteins appear to be expressed at much greater levels in the lower compared to the upper uterine segment. Moreover, the level of expression of both proteins is unaffected by the onset of parturition. In contrast, myometrial Gsα protein appears to be uniformly expressed in both lower and upper segments and is similarly down-regulated during parturition, as previously reported. The differential expression of COX-1 and -2 and connexin-43 in the uterus may allow cervical ripening before and dilatation during labor and facilitate effective propagation of contractions from fundus to cervix, which may be further facilitated by the down-regulation of Gsα at the onset of parturition.

Differential expression of Rel/NF-κB and octamer factors is a hallmark of the generation and maturation of dendritic cells

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 277-285 ◽  
Author(s):  
M. Neumann ◽  
H.-W. Fries ◽  
C. Scheicher ◽  
P. Keikavoussi ◽  
A. Kolb-Mäurer ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Differential Expression ◽  
Antigen Processing ◽  
Nuclear Translocation ◽  
Maturation Stage ◽  
Down Regulation ◽  
Immature Dendritic Cells ◽  
Monocytes And Macrophages ◽  
Induced Changes

Abstract A key feature of maturation of dendritic cells is the down-regulation of antigen-processing and up-regulation of immunostimulatory capacities. To study the differential expression of transcription factors in this process, we investigated the nuclear translocation and DNA binding of Rel/NF-κB and octamer factors during in vitro generation and maturation of dendritic cells compared with macrophage development. RelB was the only factor strongly up-regulated during the generation of both immature dendritic cells and macrophages. Cytokine-induced maturation of dendritic cells resulted in an increase in nuclear RelB, p50, p52, and especially c-Rel, whereas cytokine-treated macrophages responded poorly. This up-regulation of NF-κB factors did not correlate with lower levels of cytosolic NF-κB inhibitors, the IκBs. One IκB, Bcl-3, was strongly expressed only in mature dendritic cells. Furthermore, generation and maturation of dendritic cells led to a continuous down-regulation of the octamer factor Oct-2, whereas monocytes and macrophages displayed high Oct-2 levels. A similar pattern of maturation-induced changes in transcription factor levels was found in cultured murine epidermal Langerhans cells, suggesting a general physiological significance of these findings. Finally, this pattern of differential activation of Rel and octamer factors appears to be suitable in determining the maturation stage of dendritic cells generated by treatment with different cytokine combinations in vitro. (Blood. 2000;95:277-285)

Glutathione S-transferase omega 2 regulates cell growth and the expression of E-cadherin via post-transcriptional down-regulation of β-catenin in human esophageal squamous cells

2019 ◽  
Vol 41 (7) ◽  
pp. 875-886
Author(s):  
Masayoshi Terayama ◽  
Kazuhiko Yamada ◽  
Teruki Hagiwara ◽  
Fumika Inazuka ◽  
Takuhito Sezaki ◽  
...  
Keyword(s):  
Cell Growth ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Mapk Signaling ◽  
Membrane Localization ◽  
Esophageal Mucosa ◽  
Glutathione S Transferase ◽  
Down Regulation ◽  
Transfected Cells ◽  
E Cadherin

Abstract Glutathione S-transferase omega 2 (GSTO2), which belongs to the superfamily of GST omega class, lacks any appreciable GST activity. Although GSTO2 exhibits thioltransferase and glutathione dehydrogenase activities, its precise expression and physiological functions are still unclear. In the present study, we found that GSTO2 is exclusively expressed in the basal cell layer in Ki67-negative non-proliferative cells in the human esophageal mucosa. GSTO2 overexpression in esophageal squamous cell carcinoma (ESCC) cell lines inhibited cell growth and colony formation, and GSTO2-transfected cells formed smaller tumors in nude mice compared with mock-transfected cells. Interestingly, GSTO2 induction suppressed the expressions of E-cadherin and β-catenin at the cell–cell contact site. We quantified the phosphorylation levels of key proteins of MAPK signaling pathway and identified phosphorylation of p38. Additionally, HSP27, a downstream molecule of p38, was accelerated in GSTO2-transfected cells, unlike in mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, the expression of β-catenin and the membrane localization of E-cadherin was recovered. We next examined GSTO2 expression in 61 ESCC tissues using quantitative reverse transcription polymerase chain reaction and immunostaining. The results showed that GSTO2 mRNA and protein were significantly reduced in ESCC compared with normal tissues. When human ESCC cell lines were treated with 5-aza-2′-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant hypermethylation is the cause of the down-regulated expression. Our results indicate that GSTO2 expression inhibits the membrane localization of E-cadherin, probably by modulation of the p38 signaling pathway. Down-regulation of GSTO2 by DNA hypermethylation contributes to the growth and progression of ESCC.

Human 3α-hydroxysteroid dehydrogenase type 3: structural clues of 5α-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth

2016 ◽  
Vol 473 (8) ◽  
pp. 1037-1046 ◽  
Author(s):  
Bo Zhang ◽  
Xiao-Jian Hu ◽  
Xiao-Qiang Wang ◽  
Jean-François Thériault ◽  
Dao-Wei Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Crystal Structure ◽  
Cell Growth ◽  
Mcf7 Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Cancer Cell Growth ◽  
Down Regulation ◽  
Breast Cancer Cell Growth ◽  
Type 3 ◽  
First Time

Human 3α-HSD3 (3α-hydroxysteroid dehydrogenase type 3) plays an essential role in the inactivation of the most potent androgen 5α-DHT (5α-dihydrotestosterone). The present study attempts to obtain the important structure of 3α-HSD3 in complex with 5α-DHT and to investigate the role of 3α-HSD3 in breast cancer cells. We report the crystal structure of human 3α-HSD3·NADP+·A-dione (5α-androstane-3,17-dione)/epi-ADT (epiandrosterone) complex, which was obtained by co-crystallization with 5α-DHT in the presence of NADP+. Although 5α-DHT was introduced during the crystallization, oxidoreduction of 5α-DHT occurred. The locations of A-dione and epi-ADT were identified in the steroid-binding sites of two 3α-HSD3 molecules per crystal asymmetric unit. An overlay showed that A-dione and epi-ADT were oriented upside-down and flipped relative to each other, providing structural clues for 5α-DHT reverse binding in the enzyme with the generation of different products. Moreover, we report the crystal structure of the 3α-HSD3·NADP+·4-dione (4-androstene-3,17-dione) complex. When a specific siRNA (100 nM) was used to suppress 3α-HSD3 expression without interfering with 3α-HSD4, which shares a highly homologous active site, the 5α-DHT concentration increased, whereas MCF7 cell growth was suppressed. The present study provides structural clues for 5α-DHT reverse binding within 3α-HSD3, and demonstrates for the first time that down-regulation of 3α-HSD3 decreases MCF7 breast cancer cell growth.

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