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Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy
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Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy

Published on: April 29, 2014

Negative growth control of renal cell carcinoma cell by connexin 32: possible involvement of Her-2

Eriko Fujimoto1, Haruna Satoh, Etsuko Negishi

  • 1Faculty of Pharmaceutical Sciences, Chiba University, Chiba, Japan.

Molecular Carcinogenesis
|June 30, 2004
PubMed

Insights

Connexin 32 (Cx32) suppresses renal cell carcinoma (RCC) growth by inhibiting cell-cycle progression and Her-2 activation. Restoring Cx32 in RCC cells promotes contact inhibition and reduces tumor cell proliferation.

Area of Science:

  • Cell Biology
  • Oncology
  • Molecular Biology

Background:

  • Connexin (Cx) genes exhibit cell-specific negative growth effects on tumor cells.
  • Cx32 is downregulated in human renal cell carcinoma (RCC) and its progenitor cells.
  • The specific role of Cx32 in RCC growth control is not fully understood.

Purpose of the Study:

  • To investigate the growth-controlling function of Cx32 in human RCC cells.
  • To determine the molecular mechanisms underlying Cx32-mediated growth inhibition in RCC.

Main Methods:

  • Stable expression of Cx32 genes in Caki-2 RCC cells.
  • Assessment of cell growth control, including contact inhibition and anchorage-independent growth.
  • Cell-cycle analysis to determine the effect on G1 to S phase transition.
  • Investigation of the role of Her-2 activation using short interfering RNA (siRNA).

Main Results:

  • Cx32 expression induced contact inhibition and reduced anchorage-independent growth in Caki-2 cells.
  • Cx32 inhibited cell-cycle transition from G1 to S phase at high cell density.
  • Cx32-mediated growth control was linked to the suppression of Her-2 activation.
  • Suppression of Cx32 by siRNA led to Her-2 activation.

Conclusions:

  • Cx32 exerts negative growth control on Caki-2 RCC cells.
  • This growth inhibition is partly mediated by suppressing Her-2 activation.
  • Cx32 may serve as a potential therapeutic target for RCC.

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