Elevated expression of the colony-stimulating factor 1 (CSF1) induces prostatic intraepithelial neoplasia dependent of epithelial-Gp130
© 2022. The Author(s), under exclusive licence to Springer Nature Limited..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Oncogene - 41(2022), 9 vom: 09. Feb., Seite 1309-1323 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kwon, Oh-Joon [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 09.03.2022 Date Revised 24.10.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41388-021-02169-7 |
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| 245 | 1 | 0 | |a Elevated expression of the colony-stimulating factor 1 (CSF1) induces prostatic intraepithelial neoplasia dependent of epithelial-Gp130 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Zhang, Boyu |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Deyong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Zhicheng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Deli |e verfasserin |4 aut | |
| 700 | 1 | |a Huynh, Khoi Trung |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yiqun |e verfasserin |4 aut | |
| 700 | 1 | |a Labhart, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Sboner, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Barbieri, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Haffner, Michael C |e verfasserin |4 aut | |
| 700 | 1 | |a Creighton, Chad J |e verfasserin |4 aut | |
| 700 | 1 | |a Xin, Li |e verfasserin |4 aut | |
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