ArticleProceedings of the National Academy of Sciences of the United States of America1994
Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 246 citations in OpenAlex.
- A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: a California Cancer Consortium study.Anti-cancer drugs · 2009Trial
- A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.The Journal of experimental medicine · 2026Article
- Neuroendocrine differentiation in prostate neoplasms.Pathologie (Heidelberg, Germany) · 2025Review
- [Neuroendocrine differentiation in prostate neoplasms. German version].Pathologie (Heidelberg, Germany) · 2025Review
- Regulation of Molecular Biomarkers Associated with the Progression of Prostate Cancer.International journal of molecular sciences · 2024Review
- Glucocorticoid Receptor (GR) Activation Is Associated with Increased cAMP/PKA Signaling in Castration-Resistant Prostate Cancer.Molecular cancer therapeutics · 2024Article
- Treatment-induced stemness and lineage plasticity in driving prostate cancer therapy resistance.Cancer heterogeneity and plasticity · 2024Article
- Review
- ETS transcription factor ELF3 (ESE-1) is a cell cycle regulator in benign and malignant prostate.FEBS open bio · 2022Article
- Advances in neuroendocrine prostate cancer research: From model construction to molecular network analyses.Laboratory investigation; a journal of technical methods and pathology · 2022Review
- Role of MicroRNAs in Neuroendocrine Prostate Cancer.Non-coding RNA · 2022Review
- Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation.Journal of experimental & clinical cancer research : CR · 2022Review
- The Androgen Receptor and Its Crosstalk With the Src Kinase During Castrate-Resistant Prostate Cancer Progression.Frontiers in oncology · 2022Review
- Focus on the tumor microenvironment: A seedbed for neuroendocrine prostateFrontiers in cell and developmental biology · 2022Review
- The spectrum of neuroendocrine differentiation in prostate cancer.Prostate cancer and prostatic diseases · 2021Article
- Narrative review of challenges in the management of advanced neuroendocrine prostate cancer.Translational andrology and urology · 2021Review
- The heterogeneity of prostate cancers lacking AR activity will require diverse treatment approaches.Endocrine-related cancer · 2021Review
- Resistance to androgen receptor signaling inhibition does not necessitate development of neuroendocrine prostate cancer.JCI insight · 2021Article
- The inhibitory effect of melatonin on human prostate cancer.Cell communication and signaling : CCS · 2021Review
- Neuroendocrine cells of the prostate: Histology, biological functions, and molecular mechanisms.Precision clinical medicine · 2021Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell-like dense-core granules. Phenotypic analysis of untreated LNCaP and PC-3-M cells showed that both cell lines express markers of the neural crest including S-100, chromogranin A, pp60c-src, and neuron-specific enolase as well as the epithelial marker KS1/4 and stage-specific embryonic antigen 4. In PC-3-M cells, cAMP markedly elevated neuron-specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60c-src, and in both cell lines expression of KS1/4 and stage-specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced G1 synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogues can induce terminal differentiation, suggesting that hydrolysis-resistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.