scholarly journals Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258) and its Therapeutic Implications

2017 ◽  
Vol 10 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Shalini S. Yadav ◽  
Jinyi Li ◽  
Jennifer A. Stockert ◽  
Bryan Herzog ◽  
James O'Connor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Neuroendocrine Differentiation ◽  
Prostate Cancer Cells ◽  
Therapeutic Implications

scholarly journals Overexpression of an α1H(Cav3.2) T-type Calcium Channel during Neuroendocrine Differentiation of Human Prostate Cancer Cells

2002 ◽  
Vol 277 (13) ◽  
pp. 10824-10833 ◽  
Author(s):  
Pascal Mariot ◽  
Karine Vanoverberghe ◽  
Nathalie Lalevée ◽  
Michel F. Rossier ◽  
Natalia Prevarskaya
Keyword(s):  
Prostate Cancer ◽  
Calcium Channel ◽  
Cancer Cells ◽  
Neuroendocrine Differentiation ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells

scholarly journals Induction of entosis in prostate cancer cells by nintedanib and its therapeutic implications

2019 ◽  
Author(s):  
Junjiang Liu ◽  
Lei Wang ◽  
Yunxia Zhang ◽  
Shoubin Li ◽  
Fuzhen Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Therapeutic Implications

scholarly journals Epidermal growth factor-induced neuroendocrine differentiation and apoptotic resistance of androgen-independent human prostate cancer cells

2006 ◽  
Vol 13 (1) ◽  
pp. 181-195 ◽  
Author(s):  
S Humez ◽  
M Monet ◽  
G Legrand ◽  
G Lepage ◽  
P Delcourt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Cells ◽  
Neuroendocrine Differentiation ◽  
Calcium Entry ◽  
Calcium Overload ◽  
Prostate Cancer Cells ◽  
Epidermal Growth ◽  
Androgen Independent

Neuroendocrine differentiation (NED) has been implicated in prostate cancer progression and hormone-therapy failure. Neuroendocrine cells are non-proliferating and escape apoptotic cell death, although their origin and the causes of their apoptotic resistance have as yet been poorly elucidated. This study demonstrates a new mechanism involved in controlling NED. We report that epidermal growth factor (5–50 ng/ml) promotes neuroendocrine-like differentiation of androgen-independent DU145 prostate cancer cells. This differentiation is associated with an increase in the expression of Neuron Specific Enolase (NSE) and a reduction in cell proliferation and is blocked by inhibiting tyrosine kinase activity with genistein and with compound 56 (C56). An increase in the cAMP level, using dibutryl cAMP (db-cAMP) (1 mM) and isobutylmethylxanthine (100 μM), does not promote NED by itself, but does increase the effect of EGF on NED. In addition, EGF-induced NED protects cells from apoptosis induced with thapsigargin (1 μM) by reducing the thapsigargin-induced cytosolic calcium overload. In order to describe how EGF-induced NED protects cells against thapigargin-induced calcium overload we investigated the spatiotemporal calcium signalling linked to apoptosis. By using thapsigargin in various conditions on DU145 cells and using micro-fluorimetric calcium measurements, we show that depletion of intracellular calcium store induces apoptosis and that the amplitude and duration of the capacitive calcium entry are two apoptosis-modulating parameters. We show that protection against thapsigargin-induced apoptosis conferred by NED is achieved by reducing the amount and the speed of calcium that can be released from calcium pools, as well as modulating the amplitude of the subsequent calcium entry.

scholarly journals IL1B loss is associated with increased AR activity in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Wisam N. Awadallah ◽  
Jagpreet S. Nanda ◽  
Sarah E. Kohrt ◽  
Magdalena M Grabowska
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Cells ◽  
Marker Gene ◽  
Neuroendocrine Differentiation ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant ◽  
Expression And Activity

Castration-resistant prostate cancer represents a continuum of phenotypes, including tumors with high levels of androgen receptor (AR) expression and activity and those which do not express AR and rely on alternative pathways for survival. The process by which AR-positive prostate cancer cells and tumors lose AR expression and acquire neuroendocrine features is referred to as neuroendocrine differentiation. Numerous therapies and exposures have been demonstrated to induce neuroendocrine differentiation in vitro, including the pro-inflammatory cytokine, interleukin 1 beta (IL-1β), encoded by the gene IL1B. The purpose of our studies was to determine the relationship between the expression and activity of AR in relationship to IL-1β and IL1B in prostate cancer. We performed analysis of de-identified human clinical data and generated prostate cancer cell lines with overexpression or knockout of IL1B. In primary prostate cancer, higher expression of IL1B predicts longer time to biochemical recurrence. In metastatic castration-resistant prostate cancer, IL1B expression is decreased and inversely correlates with AR and AR-target gene expression and AR activity, while positively correlating with the neuroendocrine prostate cancer (NEPC) score and neuroendocrine marker gene expression. In vitro, we report that AR-positive castration-resistant prostate cancer cells (C4-2B, 22Rv1) secrete IL-1β, and knockout of IL1B in these cells results in increased AR activity, in the presence and absence of dihydrotestosterone (DHT). Importantly, knockout of IL1B prevented AR attrition during androgen-deprivation. Taken together, our studies demonstrate that loss of IL1B in AR-positive castration-resistant prostate cancer cells can increase and maintain AR activity in the absence of androgens, suggesting another potential mechanism of high AR activity in castration-resistant prostate cancer.

scholarly journals GRK3 is a direct target of CREB activation and regulates neuroendocrine differentiation of prostate cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (29) ◽  
pp. 45171-45185 ◽  
Author(s):  
Meixiang Sang ◽  
Mohit Hulsurkar ◽  
Xiaochong Zhang ◽  
Haiping Song ◽  
Dayong Zheng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Neuroendocrine Differentiation ◽  
Prostate Cancer Cells ◽  
Creb Activation ◽  
Direct Target
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