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Murine Prostate Micro-dissection and Surgical Castration
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Bmal1 Regulates Prostate Growth via Cell-Cycle Modulation.

Masakatsu Ueda1,2, Jin Kono1, Atsushi Sengiku1,3

  • 1Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

International Journal of Molecular Sciences
|October 14, 2022
PubMed
Summary
This summary is machine-generated.

The prostate

Keywords:
Cdkn1acircadianclockdevelopmentp21

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Chronobiology

Background:

  • The circadian clock regulates physiological processes, including organ growth.
  • The role of the peripheral prostate clock in prostate growth is not well understood.

Purpose of the Study:

  • To investigate the role of the core clock gene Bmal1 in prostate growth.
  • To elucidate the impact of the peripheral prostate clock on cell cycle regulation.

Main Methods:

  • Utilized a prostate-specific Bmal1-knockout mouse model (pBmal1 KO).
  • Employed immortalized human prostate cell lines (RWPE-1 and WPMY-1) for in vitro studies.
  • Performed cap analysis of gene expression (CAGE) and cell cycle analysis.

Main Results:

  • Bmal1 knockout in mice led to decreased prostate lobe size and reduced epithelial cell proliferation (Ki-67).
  • BMAL1 knockdown in prostate cells decreased proliferation and altered cell cycle distribution (increased G0/G1, decreased S-phase).
  • Differential gene expression related to cell cycle regulation was observed in pBmal1 KO prostates, with disrupted diurnal expression of Cdkn1a (p21).

Conclusions:

  • The core clock gene Bmal1 is integral to prostate growth through cell cycle modulation.
  • Disruption of the prostate circadian clock impacts cell proliferation and progression.
  • Findings suggest a link between circadian clock dysfunction and prostate pathologies like benign prostatic hyperplasia and cancer.