Neuroendocrine differentiation is involved in chemoresistance induced by EGF in prostate cancer cells

Li, Yuan; Chen, He Qun; Chen, Min Feng; Liu, Huai Zheng; Dai, Yuan; Lv, Hui; Zu, Xiong; Qi, Lin

doi:10.1016/j.lfs.2009.03.021

Cited by 20 publications

(21 citation statements)

References 24 publications

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“…EGF has been reported to induce NED in DU145 cells (Humez et al. , 2006; Li et al. , 2009), whereas EGFR agonists have been seen both to induce and to prevent NED in LNCaP cells (Kim et al.…”

Section: Resultsmentioning

confidence: 99%

“…3c). Recently, an NED‐inducing effect of EGF has been demonstrated also in PC3 cells (Li et al. , 2009).…”

Section: Resultsmentioning

confidence: 99%

“…Most importantly, they produce and secrete a series of neuropeptides involved in tumour proliferation, transformation and metastasis (Abrahamsson & Lilja, 1989). Recent data also suggest that the presence of NE cells in CaP induces resistance to chemotherapy (Li et al. , 2009).…”

Section: Introductionmentioning

confidence: 99%

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Androgen‐responsive and ‐unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation

Marchiani¹,

Tamburrino²,

Nesi³

et al. 2010

Int J of Andrology

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The treatment of advanced prostate cancer (CaP) with androgen deprivation therapy inevitably renders the tumours castration resistant and incurable. Under these conditions, neuroendocrine differentiation (NED) of CaP cells occurs and neuropeptides released by neuroendocrine cells facilitate tumour progression. Pharmacological strategies aiming to prevent or delay NED during androgen ablation could, therefore, increase the effectiveness of the therapy. Mechanisms and pathways inducing NED in CaP are poorly understood and data are often discordant. In the present study, we used several CaP cell lines (androgen-responsive: LNCaP, PC3-AR, 22RV1 and -irresponsive: DU145 and PC3) to evaluate NED after androgen deprivation or treatment with epidermal growth factor (EGF). NED was determined by neuron-specific enolase and chromogranin A expression and by the occurrence of morphological changes in the cells. Androgen-deprivation conditions induced NED in LNCaP and PC3-AR, but not in 22Rv1, PC3 and DU145 cells. LNCaP and PC3-AR cells also became resistant to thapsigargin-induced apoptosis. In all the AR-positive cell lines, androgen deprivation caused a decrease in androgen receptor expression indicating that it is downregulated irrespective of NED induction. Treatment with EGF induced NED in DU145 cells and the EGF receptor inhibitor gefinitib prevented the process. On the contrary, no effect of EGF was demonstrated in LNCaP or 22Rv1 cells. CaP cell lines did not respond univocally to treatments inducing NED, suggesting that studies on this topic should be performed in a wide spectrum of cell models which can be more indicative of the tumour variability in vivo.

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Section: Resultsmentioning

confidence: 99%

“…3c). Recently, an NED‐inducing effect of EGF has been demonstrated also in PC3 cells (Li et al. , 2009).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Androgen‐responsive and ‐unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation

Marchiani¹,

Tamburrino²,

Nesi³

et al. 2010

Int J of Andrology

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“…Indeed, it has been suggested that NE differentiated prostate cancer cells present within the tumor mass sustain proliferation, invasion and metastasis through the production and release of peptide hormones (3). Moreover, NED has been associated with chemotherapy resistance (4). …”

Section: Introductionmentioning

confidence: 99%

Notch Signaling Modulates Hypoxia-Induced Neuroendocrine Differentiation of Human Prostate Cancer Cells

Danza

Serio

Rosati

et al. 2012

Molecular Cancer Research

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Prostate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation has been associated with tumor progression, poor prognosis and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavourable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells, in vitro. Results exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent down regulation of Notch-mediated signalling, as demonstrated by reduced levels of the Notch target genes, Hes1 and Hey1. Neuroendocrine differentiation was promoted by attenuation of Hes1 transcription, as cells expressing a dominant negative form of Hes1 displayed increased levels of neuroendocrine markers under normoxic conditions. Although hypoxia down regulated Notch 1 and Notch 2 mRNA transcription and receptor activation also in the androgen independent cell lines, PC3 and Du145, it did not change the extent of NE differentiation in these cultures, suggesting that androgen sensitivity may be required for transdifferentiation to occur. Conclusions hypoxia induces neuroendocrine differentiation of LNCaP cells in vitro, which appears to be driven by the inhibition of Notch signalling with subsequent down-regulation of Hes1 transcription.

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“…Like IGF-I, EGF can induce an up-regulation of MMP-9 [25] and is known to be involved in the neuro-endocrine differentiation of prostate cancer cells [26,27]. To address possible additive or synergistic effects of IGF-I (300 ng/ml) and EGF (50 ng/ml) we incubated prostate cancer cells with IGF-I, EGF or a combination of IGF-I and EGF.…”

Section: Effect Of Serum Growth Factors On the Proliferation Of Prostmentioning

confidence: 99%

Attenuation of IGF-I receptor signaling inhibits serum-induced proliferation of prostate cancer cells

Himpe

Potikanond

Verdood

et al. 2011

Growth Hormone & IGF Research

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Neuroendocrine differentiation is involved in chemoresistance induced by EGF in prostate cancer cells

Cited by 20 publications

References 24 publications

Androgen‐responsive and ‐unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation

Androgen‐responsive and ‐unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation

Notch Signaling Modulates Hypoxia-Induced Neuroendocrine Differentiation of Human Prostate Cancer Cells

Attenuation of IGF-I receptor signaling inhibits serum-induced proliferation of prostate cancer cells

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