scholarly journals Expression and Function of Lysophosphatidic Acid LPA1 Receptor in Prostate Cancer Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4883-4892 ◽  
Author(s):  
Rishu Guo ◽  
Elizabeth A. Kasbohm ◽  
Puneeta Arora ◽  
Christopher J. Sample ◽  
Babak Baban ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Lysophosphatidic Acid ◽  
Cell Cycle Progression ◽  
Receptor Activation ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
And Migration

The bioactive phospholipid lysophosphatidic acid (LPA) promotes cell proliferation, survival, and migration by acting on cognate G protein-coupled receptors named LPA1, LPA2, and LPA3. We profiled gene expression of LPA receptors in androgen-dependent and androgen-insensitive prostate cancer cells and found that LPA1 gene is differentially expressed in androgen-insensitive and LPA-responsive but not androgen-dependent and LPA-resistant cells. In human prostate specimens, expression of LPA1 gene was significantly higher in the cancer compared with the benign tissues. The androgen-dependent LNCaP cells do not express LPA1 and do not proliferate in response to LPA stimulation, implying LPA1 transduces cell growth signals. Accordingly, stable expression of LPA1 in LNCaP cells rendered them responsive to LPA-induced cell proliferation and decreased their doubling time in serum. Implantation of LNCaP-LPA1 cells resulted in increased rate of tumor growth in animals compared with those tumors that developed from the wild-type cells. Growth of LNCaP cells depends on androgen receptor activation, and we show that LPA1 transduces Gαi-dependent signals to promote nuclear localization of androgen receptor and cell proliferation. In addition, treatment with bicalutamide inhibited LPA-induced cell cycle progression and proliferation of LNCaP-LPA1 cells. These results suggest the possible utility of LPA1 as a drug target to interfere with progression of prostate cancer.

Cyclin-dependent kinase 5 modulates STAT3 and androgen receptor activation through phosphorylation of Ser727 on STAT3 in prostate cancer cells

2013 ◽  
Vol 305 (8) ◽  
pp. E975-E986 ◽  
Author(s):  
Fu-Ning Hsu ◽  
Mei-Chih Chen ◽  
Kuan-Chia Lin ◽  
Yu-Ting Peng ◽  
Pei-Chi Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Receptor Activation ◽  
Cyclin Dependent Kinase ◽  
Prostate Cancer Cells ◽  
Cell Proliferation Control ◽  
Cyclin Dependent Kinase 5

Cyclin-dependent kinase 5 (Cdk5) is known to regulate prostate cancer metastasis. Our previous results indicated that Cdk5 activates androgen receptor (AR) and supports prostate cancer growth. We also found that STAT3 is a target of Cdk5 in promoting thyroid cancer cell growth, whereas STAT3 may play a role as a regulator to AR activation under cytokine control. In this study, we investigated the regulation of Cdk5 and its activator p35 on STAT3/AR signaling in prostate cancer cells. Our results show that Cdk5 biochemically interacts with STAT3 and that this interaction depends on Cdk5 activation in prostate cancer cells. The phosphorylation of STAT3 at Ser727 (p-Ser727-STAT3) is regulated by Cdk5 in cells and xenograft tumors. The mutant of STAT3 S727A reduces its interaction with Cdk5. We further show that the nuclear distribution of p-Ser727-STAT3 and the expression of STAT3-regulated genes ( junB, c-fos, c-myc, and survivin) are regulated by Cdk5 activation. STAT3 mutant does not further decrease cell proliferation upon Cdk5 inhibition, which implies that the role of STAT3 regulated by Cdk5 correlates to cell proliferation control. Interestingly, Cdk5 may regulate the interaction between STAT3 and AR through phosphorylation of Ser727-STAT3 and therefore upregulate AR protein stability and transactivation. Correspondingly, clinical evidence shows that the level of p-Ser727-STAT3 is significantly correlated with Gleason score and the levels of upstream regulators (Cdk5 and p35) as well as downstream protein (AR). In conclusion, this study demonstrates that Cdk5 regulates STAT3 activation through Ser727 phosphorylation and further promotes AR activation by protein-protein interaction in prostate cancer cells.

scholarly journals Silencing of ELK3 Induces S-M Phase Arrest and Apoptosis and Upregulates SERPINE1 Expression Reducing Migration in Prostate Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yuanshen Mao ◽  
Wenfeng Li ◽  
Bao Hua ◽  
Xin Gu ◽  
Weixin Pan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Prostate Cancer Cells ◽  
Migration Inhibition ◽  
Akt Inhibitor ◽  
Phase Arrest ◽  
M Phase ◽  
And Migration

ELK3, an ETS domain-containing transcription factor, participates in various physiological and pathological processes including cell proliferation, migration, angiogenesis, and malignant progression. However, the role of ELK3 in prostate cancer cells and its mechanism are not fully understood. The contribution of ELK3 to prostate cancer progression was investigated in the present study. We showed that silencing of ELK3 by siRNA in prostate cancer cell DU145 induced S-M phase arrest, promoted apoptosis, inhibited cell proliferation and migration in vitro, and suppressed xenograft growth in mice in vivo. In accordance with its ability to arrest cells in S-M phase, the expression of cyclin A and cyclin B was downregulated. In addition, the expression of p53 was upregulated following ELK3 knockdown, while that of antiapoptotic Bcl-2 was decreased. The migration inhibition may partly due to upregulation of SERPINE1 (a serine protease inhibitor) followed ELK3 knockdown. Consistently, downregulation of SERPINE1 resulted in a modest elimination of migration inhibition resulted from ELK3 knockdown. Furthermore, we found that the AKT signaling was activated in ELK3 knockdown cells, and treatment these cells with AKT inhibitor attenuated SERPINE1 expression induced by ELK3 silencing, suggesting that activation of AKT pathway may be one of the reasons for upregulation of SERPINE1 after ELK3 knockdown. In conclusion, modulation of ELK3 expression may control the progression of prostate cancer partly by regulating cell growth, apoptosis, and migration.

Requirement for NF-κB in interleukin-4-induced androgen receptor activation in prostate cancer cells

The Prostate ◽  
2005 ◽  
Vol 64 (2) ◽  
pp. 160-167 ◽  
Author(s):  
Soo Ok Lee ◽  
Wei Lou ◽  
Nagalakshmi Nadiminty ◽  
Xin Lin ◽  
Allen C. Gao
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Receptor Activation ◽  
Interleukin 4 ◽  
Prostate Cancer Cells ◽  
Androgen Receptor Activation

scholarly journals Cold Atmospheric Plasma Selectively Induces G0/G1 Cell Cycle Arrest and Apoptosis in AR-Independent Prostate Cancer Cells

2020 ◽  
Author(s):  
Meng Ning ◽  
Zhifa Zhang ◽  
Lihui Yu ◽  
Peiyu Han ◽  
xiaofeng Dai
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Atmospheric Plasma ◽  
Prostate Cancer Cells ◽  
Cold Atmospheric Plasma ◽  
Prostate Cancers ◽  
And Migration ◽  
Physical Plasma

Abstract BackgroundAndrogen receptor-independent prostate cancers do not respond to androgen blockage therapies and suffer from high recurrence rate. We aim to contribute to the establishment of novel therapeutic approaches against such malignancies.Methods We examined whether and how cold atmospheric plasma delivers selectivity against AR-independent prostate cancers using human normal epithelial prostatic cells PNT1A and AR-negative DU145 prostate cancer cells.ResultsWe show that cold atmospheric plasma could selectively halt cell proliferation and migration in androgen receptor-independent cells as a result of induced cell apoptosis and G0/G1 stage cell cycle arrest, and such outcomes were achieved through modulations on the MAPK and NF-kB pathways in response to physical plasma induced intracellular redox level. ConclusionOur study reports cold atmospheric plasma induced reduction on the proliferation and migration of androgen receptor-independent prostate cancer cells that offers novel therapeutic insights on the treatment of such cancers, and provides the first evidence on physical plasma induced cell cycle G0/G1 stage arrest that warrants the exploration on the synergistic use of cold atmospheric plasma and drugs such as chemotherapies in eradicating such cancer cells.

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