RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation

Nan Wu1, Dong Ren2, Su Li1

  • 1Department of Medical Genetics, Harbin Medical University, Harbin, China.

BMC Cancer
|January 12, 2018
PubMed
Abstract

Insights

Regulator of chromosome condensation 2 (RCC2) blocks Rac1 signaling, protecting cancer cells from apoptosis. Overexpression of RCC2 in lung and ovarian cancers suggests it may predict resistance to chemotherapy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Small GTP binding protein Rac1 is crucial for NADPH oxidase function and superoxide-induced cell death.
  • Regulator of chromosome condensation 2 (RCC2) inhibits Rac1 activation by binding its switch regions, preventing guanine nucleotide exchange factor (GEF) access.

Purpose of the Study:

  • To investigate the role of RCC2 in cancer cell apoptosis and its relationship with Rac1 signaling.
  • To evaluate RCC2 expression in lung and ovarian cancers.
  • To determine if RCC2 expression influences sensitivity to chemotherapeutic drugs.

Main Methods:

  • Utilized three cancer cell lines with altered RCC2 expression to assess proliferation, apoptosis, Rac1 signaling, and drug sensitivity.
  • Employed immunohistochemistry on tumor tissue arrays to study RCC2 expression in lung and ovarian cancers.

Main Results:

  • Forced RCC2 expression inhibited spontaneous and Staurosporine (STS)-induced apoptosis, while RCC2 knockdown increased STS-induced apoptosis.
  • RCC2's protective effect against apoptosis was abolished by activated Rac1, confirming its role in Rac1-mediated apoptosis.
  • RCC2 was overexpressed in 88.3% of primary lung cancers and 65.2% of ovarian cancers.
  • Tumor cells with forced RCC2 expression exhibited altered sensitivity to common chemotherapeutic drugs.

Conclusions:

  • RCC2 regulates apoptosis by inhibiting Rac1 signaling.
  • Tumor RCC2 expression may serve as a predictive marker for chemotherapeutic response.

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