Elevated expression of the colony-stimulating factor 1 (CSF1) induces prostatic intraepithelial neoplasia dependent of epithelial-Gp130.


Journal

Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562

Informations de publication

Date de publication:
02 2022
Historique:
received: 03 09 2021
accepted: 22 12 2021
revised: 06 12 2021
pubmed: 10 1 2022
medline: 11 3 2022
entrez: 9 1 2022
Statut: ppublish

Résumé

Macrophages are increased in human benign prostatic hyperplasia and prostate cancer. We generate a Pb-Csf1 mouse model with prostate-specific overexpression of macrophage colony-stimulating factor (M-Csf/Csf1). Csf1 overexpression promotes immune cell infiltration into the prostate, modulates the macrophage polarity in a lobe-specific manner, and induces senescence and low-grade prostatic intraepithelial neoplasia (PIN). The Pb-Csf1 prostate luminal cells exhibit increased stem cell features and undergo an epithelial-to-mesenchymal transition. Human prostate cancer patients with high CSF-1 expression display similar transcriptional alterations with the Pb-Csf1 model. P53 knockout alleviates senescence but fails to progress PIN lesions. Ablating epithelial Gp130 but not Il1r1 substantially blocks PIN lesion formation. The androgen receptor (AR) is downregulated in Pb-Csf1 mice. ChIP-Seq analysis reveals altered AR binding in 2482 genes although there is no significant widespread change in global AR transcriptional activity. Collectively, our study demonstrates that increased macrophage infiltration causes PIN formation but fails to transform prostate cells.

Identifiants

pubmed: 34999736
doi: 10.1038/s41388-021-02169-7
pii: 10.1038/s41388-021-02169-7
pmc: PMC8882147
mid: NIHMS1766779
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1309-1323

Subventions

Organisme : Wellcome Trust
ID : 107436
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK107436
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA190378
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK092202
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA196570
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Oh-Joon Kwon (OJ)

Department of Urology, University of Washington, Seattle, WA, 98109, USA.

Boyu Zhang (B)

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.

Deyong Jia (D)

Department of Urology, University of Washington, Seattle, WA, 98109, USA.

Li Zhang (L)

Department of Urology, University of Washington, Seattle, WA, 98109, USA.

Xing Wei (X)

Department of Urology, University of Washington, Seattle, WA, 98109, USA.

Zhicheng Zhou (Z)

Department of Urology, University of Washington, Seattle, WA, 98109, USA.

Deli Liu (D)

Sandra and Edward Meyer Cancer Center and Department of Urology, Weill Cornell Medicine, New York, NY, USA.

Khoi Trung Huynh (KT)

Department of Biology, University of Washington, Seattle, WA, 98109, USA.

Kai Zhang (K)

Department of Urology, University of Washington, Seattle, WA, 98109, USA.

Yiqun Zhang (Y)

Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Paul Labhart (P)

Active Motif, San Diego, CA, USA.

Andrea Sboner (A)

Sandra and Edward Meyer Cancer Center and Department of Urology, Weill Cornell Medicine, New York, NY, USA.

Chris Barbieri (C)

Sandra and Edward Meyer Cancer Center and Department of Urology, Weill Cornell Medicine, New York, NY, USA.

Michael C Haffner (MC)

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98109, USA.

Chad J Creighton (CJ)

Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Li Xin (L)

Department of Urology, University of Washington, Seattle, WA, 98109, USA. xin18@uw.edu.
Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA. xin18@uw.edu.

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