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Updated: Jun 28, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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AR-V7 expression facilitates accelerated G2/M phase transition in castration-resistant prostate cancer

Taruna Saini1, Parth Gupta1, Rajnikant Raut1

  • 1Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502284, India.

Experimental Cell Research
|April 11, 2024
PubMed

Insights

Androgen receptor variant 7 (AR-V7) expression fluctuates during the cell cycle, peaking in G2/M phase. The CLK1-pSRSF1 pathway critically regulates AR-V7 generation in castration resistant prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Androgen deprivation therapy (ADT) resistance in prostate cancer is often driven by the emergence of the AR-V7 splice variant.
  • Understanding the regulation of AR-V7 is crucial for developing effective therapeutic strategies against castration resistant prostate cancer (CRPC).

Purpose of the Study:

  • To investigate the cell cycle-dependent regulation of AR-V7 expression.
  • To identify key molecular players involved in AR-V7 generation during the cell cycle.

Main Methods:

  • Cell cycle analysis using flow cytometry.
  • Western blotting to detect protein levels of AR-V7, CLK1, and p-SRSF1.
  • Knockdown and overexpression experiments of CLK1 in CRPC cells.

Main Results:

  • AR-V7 expression exhibits periodic fluctuations, peaking during the G2/M phase of the cell cycle.
  • CLK1 and phosphorylated SRSF1 (p-SRSF1) expression correlate with AR-V7 levels during specific cell cycle phases.
  • CLK1 activity is essential for modulating AR-V7 levels, with kinase-deficient mutants reducing AR-V7 expression.

Conclusions:

  • AR-V7 expression is periodically regulated throughout the cell cycle.
  • The CLK1-pSRSF1 axis plays a critical role in the generation of AR-V7.
  • Targeting CLK1 activity may offer a novel therapeutic approach for CRPC by modulating AR-V7 expression.
Keywords:
AR-V7CLK1Castration-resistant prostate cancerCell cycleSR proteins

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