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

Autor: Kwon OJ; Department of Urology, University of Washington, Seattle, WA, 98109, USA., Zhang B; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA., Jia D; Department of Urology, University of Washington, Seattle, WA, 98109, USA., Zhang L; Department of Urology, University of Washington, Seattle, WA, 98109, USA., Wei X; Department of Urology, University of Washington, Seattle, WA, 98109, USA., Zhou Z; Department of Urology, University of Washington, Seattle, WA, 98109, USA., Liu D; Sandra and Edward Meyer Cancer Center and Department of Urology, Weill Cornell Medicine, New York, NY, USA., Huynh KT; Department of Biology, University of Washington, Seattle, WA, 98109, USA., Zhang K; Department of Urology, University of Washington, Seattle, WA, 98109, USA., Zhang Y; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA., Labhart P; Active Motif, San Diego, CA, USA., Sboner A; Sandra and Edward Meyer Cancer Center and Department of Urology, Weill Cornell Medicine, New York, NY, USA., Barbieri C; Sandra and Edward Meyer Cancer Center and Department of Urology, Weill Cornell Medicine, New York, NY, USA., Haffner MC; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98109, USA., Creighton CJ; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA., 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.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2022 Feb; Vol. 41 (9), pp. 1309-1323. Date of Electronic Publication: 2022 Jan 08.
DOI: 10.1038/s41388-021-02169-7
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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