Sox2 is necessary for androgen ablation-induced neuroendocrine differentiation from Pten null Sca-1+ prostate luminal cells
Prostate adenocarcinoma undergoes neuroendocrine differentiation to acquire resistance toward antihormonal therapies. The underlying mechanisms have been investigated extensively, among which Sox2 has been shown to play a critical role. However, genetic evidence in mouse models for prostate cancer to support the crucial role of Sox2 is missing. The adult mouse prostate luminal cells contain both castration-resistant Sox2-expressing Sca-1+ cells and castration-responsive Sca-1- cells. We show that both types of the luminal cell are susceptible to oncogenic transformation induced by loss of function of the tumor suppressor Pten. The tumors derived from the Sca-1+ cells are castration resistant and are more inclined to develop castration-induced neuroendocrine differentiation. Genetic ablation of Sox2 suppresses neuroendocrine differentiation but does not impact the castration-resistant property. This study provides direct genetic evidence that Sox2 is necessary for androgen ablation-induced neuroendocrine differentiation of Pten null prostate adenocarcinoma, corroborates that the lineage status of the prostate cancer cells is a determinant for its propensity to exhibit lineage plasticity, and supports that the intrinsic features of cell-of-origin for prostate cancers can dictate their clinical behaviors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Oncogene - 40(2021), 1 vom: 27. Jan., Seite 203-214 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kwon, Oh-Joon [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.04.2021 Date Revised 18.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41388-020-01526-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316788902 |
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| 245 | 1 | 0 | |a Sox2 is necessary for androgen ablation-induced neuroendocrine differentiation from Pten null Sca-1+ prostate luminal cells |
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| 500 | |a Date Revised 18.04.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Prostate adenocarcinoma undergoes neuroendocrine differentiation to acquire resistance toward antihormonal therapies. The underlying mechanisms have been investigated extensively, among which Sox2 has been shown to play a critical role. However, genetic evidence in mouse models for prostate cancer to support the crucial role of Sox2 is missing. The adult mouse prostate luminal cells contain both castration-resistant Sox2-expressing Sca-1+ cells and castration-responsive Sca-1- cells. We show that both types of the luminal cell are susceptible to oncogenic transformation induced by loss of function of the tumor suppressor Pten. The tumors derived from the Sca-1+ cells are castration resistant and are more inclined to develop castration-induced neuroendocrine differentiation. Genetic ablation of Sox2 suppresses neuroendocrine differentiation but does not impact the castration-resistant property. This study provides direct genetic evidence that Sox2 is necessary for androgen ablation-induced neuroendocrine differentiation of Pten null prostate adenocarcinoma, corroborates that the lineage status of the prostate cancer cells is a determinant for its propensity to exhibit lineage plasticity, and supports that the intrinsic features of cell-of-origin for prostate cancers can dictate their clinical behaviors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Antigens, Ly |2 NLM | |
| 650 | 7 | |a Ly6a protein, mouse |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a SOXB1 Transcription Factors |2 NLM | |
| 650 | 7 | |a Sox2 protein, mouse |2 NLM | |
| 650 | 7 | |a Tamoxifen |2 NLM | |
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| 700 | 1 | |a Jia, Deyong |e verfasserin |4 aut | |
| 700 | 1 | |a Xin, Li |e verfasserin |4 aut | |
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