Nuclear factor κB predicts poor outcome in patients with hormone-naive prostate cancer with high nuclear androgen receptor

Mackenzie, Lewis; McCall, Pamela; Hatziieremia, Sophia; Catlow, Jamie; Adams, Colin; McArdle, Peter; Seywright, Morag; Tanahill, Claire; Paul, Andrew; Underwood, Mark A.; Mackay, Simon P.; Plevin, Robin; Edwards, Joanne

doi:10.1016/j.humpath.2011.11.009

Cited by 16 publications

(13 citation statements)

References 26 publications

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“…The latter finding is commonly accepted, but the expression patterns of the AR in HN and CR PCs have been controversially discussed in the literature (Linja et al 2001, MacKenzie et al 2012. We showed that whereas most of the PC cells, independent of the ADT status, express the AR protein, CR PC cells express it at higher levels.…”

Section: Discussionmentioning

confidence: 45%

Estrogen receptor β expression and androgen receptor phosphorylation correlate with a poor clinical outcome in hormone-naïve prostate cancer and are elevated in castration-resistant disease

Zellweger¹,

Stürm²,

Rey³

et al. 2013

Endocrine-Related Cancer

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Section: Discussionmentioning

confidence: 45%

Estrogen receptor β expression and androgen receptor phosphorylation correlate with a poor clinical outcome in hormone-naïve prostate cancer and are elevated in castration-resistant disease

Zellweger¹,

Stürm²,

Rey³

et al. 2013

Endocrine-Related Cancer

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“…These observations indicate that hyperactivated NF-κB promotes HCC cell survival. Aberrant p65 phosphorylation at Ser536 is also observed in other types of human malignant tissues, not only in HCC [40–42]. Increased basal levels of p65 phosphorylation at Ser536 can thus be a mechanistical contributor to the cancer-related hyperactivation of NF-κB.…”

Section: Discussionmentioning

confidence: 99%

Isoliensinine induces dephosphorylation of NF-κB p65 subunit at Ser536 via a PP2A-dependent mechanism in hepatocellular carcinoma cells: roles of impairing PP2A/I2PP2A interaction

et al. 2016

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Our previous study discovered that isoliensinine (isolie) triggers hepatocellular carcinoma (HCC) cell apoptosis via inducing p65 dephosphorylation at Ser536 and inhibition of NF-κB. Here, we showed that isolie promoted p65/PP2A interaction in vitro and in vivo. Repression of PP2A activity or knockdown of the expression of PP2A-C (the catalytic subunit of PP2A) abrogated isolie-provoked p65 dephosphorylation. I2PP2A is an endogenous PP2A inhibitor. Isolie directly impaired PP2A/I2PP2A interaction. Knockdown of I2PP2A boosted p65/PP2A association and p65 dephosphorylation. Overexpression of I2PP2A restrained isolie-induced p65 dephosphorylation. Untransformed hepatocytes were insensitive to isolie-induced NF-κB inhibition and cell apoptosis. In these cells, basal levels of I2PP2A and p65 phosphorylation at Ser536 were lower than in HCC cells. These findings collectively indicated that isolie suppresses NF-κB in HCC cells through impairing PP2A/I2PP2A interaction and stimulating PP2A-dependent p65 dephosphorylation at Ser536.

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“…The study of phosphorylation in signal transduction events is especially important in pathways that are known to be dysregulated in disease states. Recent studies have defined a role for measuring the kinetics of phosphorylation events in not only the diagnosis/prognosis of diseases (Mackenzie et al, 2012; Sonnenblick et al, 2012; Woost et al, 2011), but also the efficacy of therapies, such as with the bcr/abl kinase inhibitor Imatinib, directed towards epigenetic alterations. (Druker et al, 2001; Hedley et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous assessment of NF-κB/p65 phosphorylation and nuclear localization using imaging flow cytometry

Maguire

O’Loughlin

Minderman

2015

Journal of Immunological Methods

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Aberrant activity of Nuclear Factor–kappaB (NF-κB) is associated with many diseases and is therapeutically targeted. Post-translational modifications, particularly phosphorylation of the RELA/p65 sub-unit, are essential for cytoplasmic to nuclear localization of NF-κB/p65 and initiation of transcription of downstream target genes. Immunoblot and phospho-flow cytometry has been used to study the relationship between phosphorylation motifs and NF-κB activation and microscopic analysis of nuclear localization of p65 is also used as a parameter for activation. The labor intensive nature of these approaches commonly limits the number of sampling points or replicates. Recent insights in the relationship between p65 phosphorylation motifs and its nuclear localization indicate that these parameters have different significance and should not be used interchangeably. In this study, we demonstrate feasibility and reproducibility of studying the relationship between p65 phosphorylation and nuclear translocation using imaging flow cytometry (IFC). TNFα- or PMA/Ionomycin-induced phosphorylation of p65 at serine 529 in cell line models and healthy donor lymphocytes served as the experimental model. IFC analysis demonstrated that expression of phosphorylated serine 529 (P-p65s529) increased rapidly following stimulation and that nuclear localization of P-p65s529 followed the nuclear localization pattern of total p65. However, in the presence of tacrolimus, P-p65s529 expression was inhibited without affecting nuclear localization of total p65. The data demonstrate the application of IFC to simultaneously assess phosphorylation of p65 and its cellular localization and the results obtained by this analysis corroborate current insights regarding the specific effect of tacrolimus on serine 529 phosphorylation.

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Nuclear factor κB predicts poor outcome in patients with hormone-naive prostate cancer with high nuclear androgen receptor

Cited by 16 publications

References 26 publications

Estrogen receptor β expression and androgen receptor phosphorylation correlate with a poor clinical outcome in hormone-naïve prostate cancer and are elevated in castration-resistant disease

Estrogen receptor β expression and androgen receptor phosphorylation correlate with a poor clinical outcome in hormone-naïve prostate cancer and are elevated in castration-resistant disease

Isoliensinine induces dephosphorylation of NF-κB p65 subunit at Ser536 via a PP2A-dependent mechanism in hepatocellular carcinoma cells: roles of impairing PP2A/I2PP2A interaction

Simultaneous assessment of NF-κB/p65 phosphorylation and nuclear localization using imaging flow cytometry

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