Different profiles of neuroendocrine cell differentiation evolve in the PC‐310 human prostate cancer model during long‐term androgen deprivation

Jongsma, Johan; Oomen, M.H.A.; Noordzij, Marinus A.; Weerden, Wytske M. van; Martens, Gerard J.M.; Kwast, Theodorus H. van der; Schröder, Fritz H.; Steenbrugge, G.J. van

doi:10.1002/pros.10049

Cited by 52 publications

(23 citation statements)

References 58 publications

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“…These results are consistent with previous studies that neuroendocrine differentiation in PC can be induced by ADT or inhibition of the AR in vitro [21–26], in PC xenografts in mice [27–31] and in patient samples [32, 33]. While a very small number of LNCaP cells survived, most of them died after 28 days of enzalutamide treatment.…”

Section: Resultssupporting

confidence: 92%

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

Zhao

Wang

et al. 2016

Oncotarget

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Enzalutamide is a second-generation anti-androgen for treatment of castration-resistant prostate cancer (CPRC). It prolongs survival of CRPC patients, but its overall survival benefit is relatively modest (4.8 months) and by 24 months most patients progress on enzalutamide. To date, however, the molecular mechanisms underlying enzalutamide resistance remain elusive. Herein, we report enzalutamide treatment-induced alterations of androgen receptor (AR)-regulated enhancer RNAs (AR-eRNAs) and their roles in enzalutamide-resistant growth and survival of CRPC cells. AR chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) and RNA-seq analyses revealed that 188 and 227 AR-eRNAs were differentially expressed in enzalutamide-resistant LNCaP and C4-2 cells, respectively. The AR-eRNAs upregulated in C4-2 cells and downregulated in LNCaP cells were selected through meta-analysis. Expression of AR-eRNAs and related mRNAs in the loci of FTO, LUZP2, MARC1 and NCAM2 were further verified by real-time RT-PCR. Silencing of LUZP2 inhibited, but silencing of MARC1 increased the growth of enzalutamide-resistant C4-2 cells. Intriguingly, meta-analysis showed that expression of LUZP2 mRNA increased in primary tumors compared to normal prostate tissues, but decreased again in metastatic CRPC. Our findings suggest that eRNA alteration profiling is a viable new approach to identify functional gene loci that may not only contribute to enzalutamide-resistant growth of CRPC, but also serve as new targets for CRPC therapy.

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Section: Resultssupporting

confidence: 92%

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

Zhao

Wang

et al. 2016

Oncotarget

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“…Radiotherapy is also widely used in prostate cancer treatment. However, once the tumor has spread, such local tumor removal has little impact on the overall outcome or course of disease (Jongsma et al, 2002). Thus, the disseminated tumors need innovative and systemic approaches.…”

Section: Prostate Cancermentioning

confidence: 99%

Role of Chemokines and Chemokine Receptors in Prostate Cancer Development and Progression

2010

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Prostate cancer (PC) is the second leading cause of cancer deaths in men in America and Western Europe. Epidemiological studies suggest that prostate cancer incidences increased in last few years in Asian. The causes or consequences of increasing trend of prostate cancer incidence are not completely known. Emerging evidences suggest that among the many risk factors, inflammation is the major risk factor for developing prostate cancer and its progression to metastasis. It is proposed that exposure to environmental factors such as infectious agents, dietary agents and saturated lipids leads to injury of the prostate due to chronic inflammation and regenerative risk factor lesions referred to as proliferative inflammatory atrophy (PIA). These phenomena predominantly control by a number of proinflammatory macro molecules such as chemokines, and their receptors. Some recent studies suggest that many of these pro-inflammatory chemokines and their receptors are the products of protooncogenes in many cancers including that of the prostate. This review will focus on the current biology of chemokines and chemokine receptors in prostate cancer. An understanding of this axis may enable researchers to develop targeted strategies for prostate cancer.

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“…Increasing numbers of NE cells are thought to originate by clonal progression under the selection pressure of therapy6 and support for this theory is provided by animal studies in which a probasin-large T antigen transgenic mouse line developed prostate adenocarcinoma and NE carcinoma after being linked with SV40 T-antigen. In this study, higher grade disease developed progressively into greater NE differentiation and a high percentage of metastases 7…”

Section: Discussionmentioning

confidence: 99%

A rare case of large cell neuroendocrine carcinoma

et al. 2014

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SUMMARYWe present a very rare case of de novo large cell neuroendocrine carcinoma (LCNEC) of the prostate in an 84-year-old man on a background of high grade, superficially invasive transitional cell carcinoma of the bladder. Pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate are thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing neuroendocrine differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease and a worse prognosis. BACKGROUND

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Different profiles of neuroendocrine cell differentiation evolve in the PC‐310 human prostate cancer model during long‐term androgen deprivation

Cited by 52 publications

References 58 publications

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

Role of Chemokines and Chemokine Receptors in Prostate Cancer Development and Progression

A rare case of large cell neuroendocrine carcinoma

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