KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation of colorectal cancer cell lines

Yasuhiro Yoshida, Toshiyuki Tsunoda, Keiko Doi, Yoko Tanaka, Takahiro Fujimoto, Takashi Machida, Takeharu Ota, Midori Koyanagi, Yasuo Takashima, Takehiko Sasazuki, Masahide Kuroki, Akinori Iwasaki, Senji Shirasawa

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Background: We previously investigated the mRNA expression of colorectal cancer cell lines via a microarray analysis and found several genes that were significantly up-regulated by oncogenic KRAS under serum-starved conditions. Of these genes, we focused on ribonucleotide reductase M2 (RRM2), which was reported to be associated with DNA synthesis. Materials and Methods: Cell proliferation and colony formation assays were performed using HCT116 cells transfected with lentiviral RRM2-shRNAs. Results: Under serum-starved conditions, the expression level of RRM2 protein increased in HCT116 cells compared to HKe3 cells (HCT116 cells with a disruption in oncogenic KRAS), and the re-expression of KRAS in HKe3 cells induced the expression of RRM2. Both the cell proliferation under serum-depleted conditions and the anchorage- independent growth were impaired by the reduction of RRM2 protein expression. Conclusion: RRM2 represents a novel therapeutic target, thus highlighting the potential utility of RRM2 inhibitors in colorectal cancer with oncogenic KRAS.

Original languageEnglish
Pages (from-to)2535-2539
Number of pages5
JournalAnticancer research
Issue number7
Publication statusPublished - Jul 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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