Ectopic expression of CC chemokine receptor 7 promotes prostate cancer cells metastasis via Notch1 signaling

2018 ◽  
Vol 120 (6) ◽  
pp. 9639-9647 ◽  
Author(s):  
Ruoyang Du ◽  
Guanlin Tang ◽  
Zhaobing Tang ◽  
Youlin Kuang
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Chemokine Receptor ◽  
Ectopic Expression ◽  
Prostate Cancer Cells ◽  
Cc Chemokine ◽  
Notch1 Signaling ◽  
Cc Chemokine Receptor 7

scholarly journals DNMT1 and DNMT3B regulate tumorigenicity of human prostate cancer cells by controlling RAD9 expression through targeted methylation

2020 ◽  
Author(s):  
Aiping Zhu ◽  
Kevin M Hopkins ◽  
Richard A Friedman ◽  
Joshua D Bernstock ◽  
Constantinos G Broustas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Dna Methyltransferases ◽  
Prostate Cancer Cells ◽  
Normal Prostate ◽  
Prostate Tumorigenesis ◽  
Du145 Cells ◽  
Cpg Hypermethylation ◽  
High Level

Abstract Prostate cancer is the second most common type of cancer and the second leading cause of cancer death in American men. RAD9 stabilizes the genome, but prostate cancer cells and tumors often have high quantities of the protein. Reduction of RAD9 level within prostate cancer cells decreases tumorigenicity of nude mouse xenographs and metastasis phenotypes in culture, indicating that RAD9 overproduction is essential for the disease. In prostate cancer DU145 cells, CpG hypermethylation in a transcription suppressor site of RAD9 intron 2 causes high-level gene expression. Herein, we demonstrate that DNA methyltransferases DNMT1 and DNMT3B are highly abundant in prostate cancer cells DU145, CWR22, LNCaP and PC-3; yet, these DNMTs bind primarily to the transcription suppressor in DU145, the only cells where methylation is critical for RAD9 regulation. For DU145 cells, DNMT1 or DNMT3B shRNA reduced RAD9 level and tumorigenicity, and RAD9 ectopic expression restored this latter activity in the DNMT knockdown cells. High levels of RAD9, DNMT1, DNMT3B and RAD9 transcription suppressor hypermethylation were significantly correlated in prostate tumors, and not in normal prostate tissues. Based on these results, we propose a novel model where RAD9 is regulated epigenetically by DNMT1 and DNMT3B, via targeted hypermethylation, and that consequent RAD9 overproduction promotes prostate tumorigenesis.

scholarly journals Androgen and Its Receptor Promote Bax-Mediated Apoptosis

2006 ◽  
Vol 26 (5) ◽  
pp. 1908-1916 ◽  
Author(s):  
Yuting Lin ◽  
John Kokontis ◽  
Fangming Tang ◽  
Bradley Godfrey ◽  
Shutsung Liao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Transcription Activation ◽  
Prostate Cancer Cells ◽  
Small Interference Rna ◽  
Apoptotic Death ◽  
Apoptosis Inhibition ◽  
Induced Apoptosis ◽  
Interference Rna

ABSTRACT Androgen and its receptor (AR) have been reported to have pro- or antiapoptotic functions. However, the underlying molecular mechanism is incompletely understood. We report here that androgen and AR promote Bax-mediated apoptosis in prostate cancer cells. UV irradiation and ectopic expression of Bax induce apoptosis in AR-positive, but not AR-negative prostate cancer cells. UV- and Bax-induced apoptosis is abrogated in AR-positive cells that express small interference RNA (siRNA) of AR and is sensitized by reintroduction of AR into AR-negative cells. Although AR is able to promote Bax-mediated apoptosis independently of androgen, the promotion by AR can be further potentiated by androgen via AR-dependent transcription activation. AR is essential for the translocation of Bax to mitochondria in UV- or Bax-induced apoptosis. Inhibition of Bax expression by Bax siRNA suppresses UV-induced apoptosis in AR-positive cells. In addition, introduction of AR into AR-negative prostate cancer cells upregulates expression levels of the BH3-only protein Noxa, whereas inhibition of Noxa expression reduces the promotion by AR on UV-induced apoptosis. Thus, our results reveal a novel cross talk between the androgen/AR hormonal signaling pathway and the intrinsic apoptotic death pathway that determines the sensitivity of stress-induced apoptosis in prostate cancer cells.

scholarly journals GADD45γ: a New Vitamin D-Regulated Gene that Is Antiproliferative in Prostate Cancer Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4654-4664 ◽  
Author(s):  
Omar Flores ◽  
Kerry L. Burnstein
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cell Cycle ◽  
Vitamin D ◽  
Androgen Receptor ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits proliferation of normal and malignant prostate epithelial cells at least in part through inhibition of G1 to S phase cell cycle progression. The mechanisms of the antiproliferative effects of 1,25-(OH)2D3 have yet to be fully elucidated but are known to require the vitamin D receptor. We previously developed a 1,25-(OH)2D3-resistant derivative of the human prostate cancer cell line, LNCaP, which retains active vitamin D receptors but is not growth inhibited by 1,25-(OH)2D3. Gene expression profiling revealed two novel 1,25-(OH)2D3-inducible genes, growth arrest and DNA damage-inducible gene gamma (GADD45γ) and mitogen induced gene 6 (MIG6), in LNCaP but not in 1,25-(OH)2D3-resistant cells. GADD45γ up-regulation was associated with growth inhibition by 1,25-(OH)2D3 in human prostate cancer cells. Ectopic expression of GADD45γ in either LNCaP or ALVA31 cells resulted in G1 accumulation and inhibition of proliferation equal to or greater than that caused by 1,25-(OH)2D3 treatment. In contrast, ectopic expression of MIG6 had only minimal effects on cell cycle distribution and proliferation. Whereas GADD45γ has been shown to be induced by androgens in prostate cancer cells, up-regulation of GADD45γ by 1,25-(OH)2D3 was not dependent on androgen receptor signaling, further refuting a requirement for androgens/androgen receptor in vitamin D-mediated growth inhibition. These data introduce two novel 1,25-(OH)2D3-regulated genes and establish GADD45γ as a growth-inhibitory protein in prostate cancer. Furthermore, the induction of GADD45γ gene expression by 1,25-(OH)2D3 may mark therapeutic response in prostate cancer.

1620 THE TERE1(UBIAD1) PROTEIN REDUCES CHOLESTEROL IN C81-LNCAP PROSTATE CANCER CELLS: INDUCTION BY 1,25-OH VITAMIN D3 OR ECTOPIC EXPRESSION

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
William Fredericks ◽  
Jorge Sepulveda ◽  
Priti Lal ◽  
John Tomaszewski ◽  
Terrence McGarvey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Vitamin D3 ◽  
Ectopic Expression ◽  
Prostate Cancer Cells

scholarly journals The Hippo Pathway Effector YAP Regulates Motility, Invasion, and Castration-Resistant Growth of Prostate Cancer Cells

2015 ◽  
Vol 35 (8) ◽  
pp. 1350-1362 ◽  
Author(s):  
Lin Zhang ◽  
Shuping Yang ◽  
Xingcheng Chen ◽  
Seth Stauffer ◽  
Fang Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Prostate Tumors ◽  
Castration Resistant

Yes-associated protein (YAP) is an effector of the Hippo tumor suppressor pathway. The functional significance of YAP in prostate cancer has remained elusive. In this study, we first show that enhanced expression of YAP is able to transform immortalized prostate epithelial cells and promote migration and invasion in both immortalized and cancerous prostate cells. We found that YAP mRNA was upregulated in androgen-insensitive prostate cancer cells (LNCaP-C81 and LNCaP-C4-2 cells) compared to the level in androgen-sensitive LNCaP cells. Importantly, ectopic expression of YAP activated androgen receptor signaling and was sufficient to promote LNCaP cells from an androgen-sensitive state to an androgen-insensitive statein vitro, and YAP conferred castration resistancein vivo. Accordingly, YAP knockdown greatly reduced the rates of migration and invasion of LNCaP-C4-2 cells and under androgen deprivation conditions largely blocked cell division in LNCaP-C4-2 cells. Mechanistically, we found that extracellular signal-regulated kinase–ribosomal s6 kinase signaling was downstream of YAP for cell survival, migration, and invasion in androgen-insensitive cells. Finally, immunohistochemistry showed significant upregulation and hyperactivation of YAP in castration-resistant prostate tumors compared to their levels in hormone-responsive prostate tumors. Together, our results identify YAP to be a novel regulator in prostate cancer cell motility, invasion, and castration-resistant growth and as a potential therapeutic target for metastatic castration-resistant prostate cancer (CRPC).

scholarly journals Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT

2020 ◽  
Author(s):  
Yao Zhao ◽  
Chenchen Cai ◽  
Lubing Shi ◽  
Jiwei Wang ◽  
Miaomiao Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Eph Receptor ◽  
Prostate Cancer Metastasis

Abstract Background Ephrin-A2, a member of the Eph receptor subgroup, is used in diagnosing and determining the prognosis of prostate cancer. However, the role of ephrin-A2 in prostate cancer is still unclear. Methods We established stable clones overexpressing or silencing ephrin-A2 from prostate cancer cells. Then, CCK-8 was used in analyzing the proliferation ability of cells. CD31 staining was used in evaluating angiogenesis. Migration and invasion assay were conducted in vivo and in vitro. The expression of EMT-related markers was evaluated in prostate cancer cells through Western blotting. Results We revealed that the ectopic expression of ephrin-A2 in prostate cancer cells facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo and that the silencing of ephrin-A2 completely reversed this effect. Although ephrin-A2 did not affect tumor cell proliferation in vitro, ephrin-A2 significantly promoted primary tumor growth in vivo. Furthermore, to determine the biological function of ephrin-A2, we assayed the expression of EMT-related markers in stable established cell lines. Results showed that the overexpression of ephrin-A2 in prostate cancer cells down-regulated the expression of epithelial markers (ZO-1, E-cadherin, and claudin-1) and up-regulated the expression of mesenchymal markers (N-cadherin, β-catenin, vimentin, Slug, and Snail), but the knocking out of ephrin-A2 opposed the effects on the expression of EMT markers. Conclusions These findings indicate that ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT and may be a potentially therapeutic target in metastatic prostate cancer.

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