JunD Is Required for Proliferation of Prostate Cancer Cells and Plays a Role in Transforming Growth Factor-β (TGF-β)-induced Inhibition of Cell Proliferation

Millena, Ana C.; Vo, BaoHan T.; Khan, Shafiq A.

doi:10.1074/jbc.m116.714899

Cited by 33 publications

(51 citation statements)

References 82 publications

(78 reference statements)

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“…We have previously shown that TGF‐β exerts differential effects on cell proliferation of different prostate cancer cell lines . TGF‐β isoforms caused a significant inhibition of cell proliferation in DU145 cells (Figure A).…”

Section: Resultsmentioning

confidence: 82%

“…In previous studies, TGF‐β has been shown to exert differential biological effects in different prostate cancer‐derived cell lines . To confirm these studies, we first determined the effects of TGF‐β1 and TGF‐β3 (5 ng/mL) and the combination of both (TGF‐β1 and TGF‐β3) on cell proliferation in DU145 prostate cancer cells (Figure A).…”

Section: Resultsmentioning

confidence: 88%

“…On the other hand, TGF‐β1 and TGF‐β3 isoforms have similar effects on proliferation of different prostate cancer cell lines . Both isoforms inhibit proliferation in DU145 cells, however, PC3 cells do not respond to the inhibitory effects of either of the two isoforms, which indicates TGF‐β differential effects on cell proliferation depending on the context of the cell. The specific roles of individual TGF‐β isoforms in development and progression of prostate cancer in vivo have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Differential role of PTEN in transforming growth factor β (TGF‐β) effects on proliferation and migration in prostate cancer cells

2018

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Background Transforming growth factor -β (TGF-β) acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. PTEN inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. We investigated possible role(s) of PTEN in TGF-β effects on proliferation and migration in prostate cancer cells. Methods Expression of PTEN mRNA and proteins were determined using RT-PCR and western blotting in RWPE-1 and DU145 cells. We also studied the role of PTEN in TGFβ effects on cell proliferation and migration in DU145 cells after transient silencing of endogenous PTEN. Conversely, we determined the role of PTEN in cell proliferation and migration after over-expression of PTEN in PC3 cells which lack endogenous PTEN. Results TGF-β1 and TGF-β3 had no effect on PTEN mRNA levels but both isoforms increased PTEN protein levels in DU145 and RWPE1 cells indicating that PTEN may mediate TGF-β effects on cell proliferation. Knockdown of PTEN in DU145 cells resulted in significant increase in cell proliferation which was not affected by TGF-β isoforms. PTEN overexpression in PC3 cells inhibited cell proliferation. Knockdown of endogenous PTEN enhanced cell migration in DU145 cells, whereas PTEN overexpression reduced migration in PC3 cells and reduced phosphorylation of AKT in response to TGF-β. Conclusion We conclude that PTEN plays a role in inhibitory effects of TGFβ on cell proliferation whereas its absence may enhance TGF-β effects on activation of PI3-kinase pathway and cell migration.

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Section: Resultsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Differential role of PTEN in transforming growth factor β (TGF‐β) effects on proliferation and migration in prostate cancer cells

2018

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“…TFs with higher cell specificity relate to biological processes displaying highly variable regulatory activity across conditions, such as pluripotency, cell cycle regulation, tumor suppression or tumorigenesis, including EP300 (Kim et al, 2013), BCL11A (Khaled et al, 2015, Dong et al, 2017, ZBTB33 (Pozner et al, 2016) and JUND (Caffarel et al, 2008, Millena et al, 2016. On the contrary, TFs with more constant roles such as NR2C2 (O'Geen et al, 2010) show very little difference between cell types.…”

Section: Quantification Of Tf Regulation Rewiring Using Topic Weightsmentioning

confidence: 99%

TopicNet: a framework for measuring transcriptional regulatory network change

Lou

Kong

et al. 2019

Preprint

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Next generation sequencing data highlights comprehensive and dynamic changes in the human gene regulatory network. Moreover, changes in regulatory network connectivity (network "rewiring") manifest different regulatory programs in multiple cellular states. However, due to the dense and noisy nature of the connectivity in regulatory networks, directly comparing the gains and losses of targets of key TFs is not that informative. Thus, here, we seek a abstracted lowerdimensional representation to understand the main features of network change. In particular, we propose a method called TopicNet that applies latent Dirichlet allocation (LDA) to extract meaningful functional topics for a collection of genes regulated by a TF. We then define a rewiring score to quantify the large-scale changes in the regulatory network in terms of topic change for a TF. Using this framework, we can pinpoint particular TFs that change greatly in network connectivity between different cellular states. This is particularly relevant in oncogenesis. Also, incorporating gene-expression data, we define a topic activity score that gives the degree that a topic is active in a particular cellular state. Furthermore, we show how activity differences can highlight differential survival in certain cancers.

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“…The most significantly differentially methylated CpG locus is found within the second intron of the CBX2 gene ( Figure 5). This CpG site overlaps with two different enhancer marks (H3K4me1 and H3K27ac), promoter marks (H3K4me2 and H3K4me3), transcriptional activation (H3K9ac) and transcriptional elongation (H4K20me1) marks, as well as with a transcription factor, JunD, that promotes cancer cell proliferation 31 . In addition, H4K20me1 is absent in the first exon and promoter region, suggesting that transcription of this gene may begin or be regulated through interactions within the 2 nd intron.…”

Section: Low Levels Of Dna Cpg Methylation In Breast Cancer Cell Enhamentioning

confidence: 99%

A novel approach to modeling transcriptional heterogeneity identifies the oncogene candidate CBX2 in invasive breast carcinoma

Piqué

Montagna

Greally

et al. 2018

Preprint

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Word limit: 150)Oncogenes promote the development of and serve as therapeutic targets against subsets of cancers. Here, a new statistical approach that captures transcriptional heterogeneity in tumor and adjacent normal (i.e. tumor-free) mRNA expression profiles was developed to identify oncogene candidates that were overexpressed in a subset of breast tumors. Intronic DNA methylation was strongly associated with the overexpression of chromobox 2 (CBX2), an oncogene candidate that was identified using our method but not through prior analytical approaches. CBX2 overexpression in breast tumors was associated with the upregulation of genes involved in cell cycle progression and is associated with poorer 5-year survival. The predicted function of CBX2 was confirmed in vitro providing the first experimental evidence that CBX2 promotes breast cancer cell growth. Modeling mRNA expression heterogeneity in tumors is a novel powerful approach with the potential to uncover therapeutic targets that benefit subsets of cancer patients.

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JunD Is Required for Proliferation of Prostate Cancer Cells and Plays a Role in Transforming Growth Factor-β (TGF-β)-induced Inhibition of Cell Proliferation

Cited by 33 publications

References 82 publications

Differential role of PTEN in transforming growth factor β (TGF‐β) effects on proliferation and migration in prostate cancer cells

Differential role of PTEN in transforming growth factor β (TGF‐β) effects on proliferation and migration in prostate cancer cells

TopicNet: a framework for measuring transcriptional regulatory network change

A novel approach to modeling transcriptional heterogeneity identifies the oncogene candidate CBX2 in invasive breast carcinoma

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