Dominant-negative Rac1 suppresses Ras-induced apoptosis possibly through activation of NFκB in Ha-ras oncogene-transformed NIH/3T3 cells

Chao Kai Chou, Kuo Hsuan Liang, Ching Chang Tzeng, Guan Cheng Huang, Jih I. Chuang, Tsuey Yu Chang, Hsiao Sheng Liu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We investigated the involvement of Rac1 in Ha-ras-overexpression-induced apoptosis using a murine NIH/3T3-derived cell line (designated 7-4), which contains an inducible Ha-ras oncogene under the regulation of Escherichia coli lac operator-repressor system. Ha-ras overexpression was induced by isopropyl β-d-thiogalactoside (IPTG). To reveal the role of endogenous Rac1, the dominant negative Rac1Asn17 gene was transfected into the 7-4 cells. Using two cell lines 7-4 Racd2 and 7-4 Racd3 (7-4 derivates) stably expressing Rac1Asn17, we demonstrate that suppression of Rac1 activity blocked Ha-ras-overexpression-induced apoptosis under a serum-depleted condition, indicating that Rac1 activity is required for a Ras-mediated apoptosis pathway. Cell-cycle analysis revealed that dominant-negative Rac1 partially shifted cell population from S-phase to G0/G1 phase in the cells overexpressing Ha-ras. In contrast to other reports, we showed activation of the transcription factor NFκB in the two cell lines expressing dominant-negative Rac1. All together, our results demonstrate that Ha-ras-overexpression- induced apoptosis can be blocked by dominant-negative Rac1, possibly through decreased S-phase accumulation and increased NFκB activity.

Original languageEnglish
Pages (from-to)1823-1829
Number of pages7
JournalLife Sciences
Volume78
Issue number16
DOIs
Publication statusPublished - 2006 Mar 13

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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