Related Experiment Video
Updated: Jul 2, 2026

RhoC GTPase Activation Assay
Published on: August 22, 2010
Rho/ROCK/actin signaling regulates membrane androgen receptor induced apoptosis in prostate cancer cells
Natalia Papadopoulou1, Ioannis Charalampopoulos, Konstantinos Alevizopoulos
1Department of Biochemistry, University of Crete Medical School, GR-71110 Heraklion, Greece.
Abstract:
In this study we describe a novel Rho small GTPase dependent pathway that elicits apoptotic responses controlled by actin reorganization in hormone-sensitive LNCaP- and hormone insensitive DU145-prostate cancer cells stimulated with membrane androgen receptor selective agonists. Using an albumin-conjugated steroid, testosterone-BSA, we now show significant induction of actin polymerization and apoptosis that can be reversed by actin disrupting agents in both cell lines. Testosterone-BSA triggered RhoA/B and Cdc42 activation in DU145 cells followed by stimulation of downstream effectors ROCK, LIMK2 and ADF/destrin. Furthermore, dominant-negative RhoA, RhoB or Cdc42 mutants or pharmacological inhibitors of ROCK inhibited both actin organization and apoptosis in DU145 cells. Activation of RhoA/B and ROCK was also implicated in membrane androgen receptor-dependent actin polymerization and apoptosis in LNCaP cells. Our findings suggest that Rho small GTPases are major membrane androgen receptor effectors controlling actin reorganization and apoptosis in prostate cancer cells.
Insights
This study reveals a new pathway where Rho GTPases control actin reorganization and apoptosis in prostate cancer cells. This pathway is activated by membrane androgen receptor agonists, impacting both hormone-sensitive and insensitive cancer cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Prostate cancer cells exhibit varying sensitivity to hormones.
- Actin reorganization plays a role in cellular processes, including apoptosis.
- Membrane androgen receptors (mARs) are involved in prostate cancer cell signaling.
Purpose of the Study:
- To investigate a novel Rho GTPase-dependent pathway.
- To determine the role of actin reorganization in apoptosis.
- To explore the effects of mAR agonists on prostate cancer cells.
Main Methods:
- Utilized hormone-sensitive (LNCaP) and insensitive (DU145) prostate cancer cell lines.
- Stimulated cells with testosterone-BSA, a membrane-impermeable androgen agonist.
- Assessed actin polymerization, apoptosis, and Rho GTPase activation (RhoA/B, Cdc42) and downstream effectors (ROCK, LIMK2, ADF/destrin).
- Employed dominant-negative mutants and pharmacological inhibitors.
Main Results:
- Testosterone-BSA induced actin polymerization and apoptosis in both cell lines, reversible by actin-disrupting agents.
- Activated RhoA/B and Cdc42, leading to downstream effector stimulation in DU145 cells.
- Inhibition of RhoA/B, Cdc42, or ROCK blocked testosterone-BSA-induced actin organization and apoptosis.
- RhoA/B and ROCK activation were implicated in mAR-dependent processes in LNCaP cells.
Conclusions:
- Rho small GTPases are key effectors of membrane androgen receptors.
- These GTPases control actin reorganization and apoptosis in prostate cancer cells.
- The identified pathway is relevant to both hormone-sensitive and hormone-insensitive prostate cancers.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
The JAK-STAT Signaling Pathway
Amplifying Signals via Enzymatic Cascade
MAPK Signaling Cascades
Regulation of the Unfolded Protein Response
