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ResearchIn-Press PreviewCell biologyOncology Open Access | 10.1172/JCI194727

Multiomic assessments of LNCaP and derived cell strains reveal determinants of prostate cancer pathobiology

Arnab Bose,1 Armand Bankhead III,1 Ilsa Coleman,1 Thomas Persse,1 Wanting Han,1 Patricia Galipeau,1 Brian Hanratty,1 Tony Chu,1 Jared Lucas,1 Dapei Li,1 Rabeya Bilkis,1 Pushpa Itagi,1 Sajida Hassan,2 Mallory Beightol,2 Minjeong Ko,1 Ruth Dumpit,1 Michael Haffner,1 Colin Pritchard,2 Gavin Ha,1 and Peter S. Nelson1

1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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1Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

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Published September 16, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI194727.
Copyright © 2025, Bose et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 16, 2025 - Version history
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Abstract

A cornerstone of research to improve cancer outcomes involves studies of model systems to identify causal drivers of oncogenesis, understand mechanisms leading to metastases, and develop new therapeutics. While most cancer types are represented by large cell line panels that reflect diverse neoplastic genotypes and phenotypes found in patients, prostate cancer is notable for a very limited repertoire of models that recapitulate the pathobiology of human disease. Of these, Lymph node carcinoma of the prostate (LNCaP) has served as the major resource for basic and translational studies. Here, we delineated the molecular composition of LNCaP and multiple substrains through analyses of whole genome sequences, transcriptomes, chromatin structure, AR cistromes, and functional studies. Our results determined that LNCaP exhibits substantial subclonal diversity, ongoing genomic instability and phenotype plasticity. While several oncogenic features were consistently present across strains, others were unexpectedly variable such as ETV1 expression, Y chromosome loss, a reliance on WNT and glucocorticoid receptor activity, and distinct AR alterations maintaining AR pathway activation. These results document the inherent molecular heterogeneity and ongoing genomic instability that drive diverse prostate cancer phenotypes and provide a foundation for the accurate interpretation and reproduction of research findings.

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  • Version 1 (September 16, 2025): In-Press Preview
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