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Membrane androgen receptor sensitive Na+/H+ exchanger activity in prostate cancer cells

Soumya Chatterjee1, Sebastian Schmidt1, Stella Pouli2

  • 1Department of Physiology, University of Tübingen, Germany.

FEBS Letters
|March 11, 2014
PubMed

Insights

Membrane androgen receptor (mAR) activation by testosterone albumin conjugates (TAC) suppresses tumor growth. This process involves activating Na+/H+-exchangers (NHE) via SGK1 and ROCK signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Membrane androgen receptors (mAR) are present in various tumors.
  • mAR activation by testosterone albumin conjugates (TAC) inhibits tumor progression.
  • mAR signaling pathways include PI3K, ROCK, and SGK1, influencing cellular functions.

Purpose of the Study:

  • To investigate the role of mAR activation in regulating cellular pH and volume in cancer cells.
  • To elucidate the specific signaling molecules involved in mAR-mediated effects on Na+/H+-exchangers (NHE).

Main Methods:

  • Prostate cancer cells were used to measure cytosolic pH (pHi) and NHE activity.
  • Fluorescence-based assays and ammonium pulse techniques were employed.
  • The effects of TAC were assessed in the presence of specific inhibitors for NHE1, SGK1, and ROCK.

Main Results:

  • TAC significantly increased pHi and NHE activity in prostate cancer cells.
  • These effects were blocked by cariporide (NHE1 inhibitor), SGK1 inhibitors, and ROCK inhibitors.
  • TAC also increased cell volume and actin polymerization, which were abolished by cariporide.

Conclusions:

  • mAR activation stimulates cariporide-sensitive Na+/H+-exchangers.
  • This activation is dependent on SGK1 and ROCK activity.
  • mAR signaling influences cell volume and actin dynamics through NHE activation.
Keywords:
ActinCytosolic pHEMD638683Na(+)/H(+) exchangerROCKSGK1Y-27632

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