Aurora-A overexpression enhances cell-aggregation of Ha-ras transformants through the MEK/ERK signaling pathway.

Ya Shih Tseng, Jenq Chang Lee, Chi Ying F. Huang, Hsiao Sheng Liu

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND: Overexpression of Aurora-A and mutant Ras (RasV12) together has been detected in human bladder cancer tissue. However, it is not clear whether this phenomenon is a general event or not. Although crosstalk between Aurora-A and Ras signaling pathways has been reported, the role of these two genes acting together in tumorigenesis remains unclear. METHODS: Real-time PCR and sequence analysis were utilized to identify Ha- and Ki-ras mutation (Gly -> Val). Immunohistochemistry staining was used to measure the level of Aurora-A expression in bladder and colon cancer specimens. To reveal the effect of overexpression of the above two genes on cellular responses, mouse NIH3T3 fibroblast derived cell lines over-expressing either RasV12 and wild-type Aurora-A (designated WT) or RasV12 and kinase-inactivated Aurora-A (KD) were established. MTT and focus formation assays were conducted to measure proliferation rate and focus formation capability of the cells. Small interfering RNA, pharmacological inhibitors and dominant negative genes were used to dissect the signaling pathways involved. RESULTS: Overexpression of wild-type Aurora-A and mutation of RasV12 were detected in human bladder and colon cancer tissues. Wild-type Aurora-A induces focus formation and aggregation of the RasV12 transformants. Aurora-A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK, ERK of WT cells. Finally, the Ras/MEK/ERK signaling pathway is responsible for Aurora-A induced aggregation of the RasV12 transformants. CONCLUSION: Wild-type-Aurora-A enhances focus formation and aggregation of the RasV12 transformants and the latter occurs through modulating the Ras/MEK/ERK signaling pathway.

Original languageEnglish
Number of pages1
JournalBMC cancer
Volume9
DOIs
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

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