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  • [Oncogene.] Sox2 is necessary for androgen ablation-induced neuroendocrine differentiation from Pten null Sca-1 + prostate luminal cells

    University of Washington / 권오준, Li Xin*

  • 출처
    Oncogene.
  • 등재일
    2021 Jan
  • 저널이슈번호
    40(1):203-214. doi: 10.1038/s41388-020-01526-2. Epub 2020 Oct 27.
  • 내용

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    Abstract
    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.

     

     

    Affiliations

    Oh-Joon Kwon  1 , Li Zhang  1 , Deyong Jia  1 , Li Xin  2   3
    1 Department of Urology, University of Washington, Seattle, WA, 98109, USA.
    2 Department of Urology, University of Washington, Seattle, WA, 98109, USA. xin18@uw.edu.
    3 Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA. xin18@uw.edu.

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