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

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

Institute for Advanced Study

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	2535-2539
Number of pages	5
Journal	Anticancer research
Volume	31
Issue number	7
Publication status	Published - Jul 2011

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

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KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation of colorectal cancer cell lines. / Yoshida, Yasuhiro; Tsunoda, Toshiyuki; Doi, Keiko; Tanaka, Yoko; Fujimoto, Takahiro; Machida, Takashi; Ota, Takeharu; Koyanagi, Midori; Takashima, Yasuo; Sasazuki, Takehiko; Kuroki, Masahide; Iwasaki, Akinori; Shirasawa, Senji.

In: Anticancer research, Vol. 31, No. 7, 07.2011, p. 2535-2539.

Research output: Contribution to journal › Article › peer-review

Yoshida, Yasuhiro ; Tsunoda, Toshiyuki ; Doi, Keiko ; Tanaka, Yoko ; Fujimoto, Takahiro ; Machida, Takashi ; Ota, Takeharu ; Koyanagi, Midori ; Takashima, Yasuo ; Sasazuki, Takehiko ; Kuroki, Masahide ; Iwasaki, Akinori ; Shirasawa, Senji. / KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation of colorectal cancer cell lines. In: Anticancer research. 2011 ; Vol. 31, No. 7. pp. 2535-2539.

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abstract = "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.",

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

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AU - Yoshida, Yasuhiro

AU - Tsunoda, Toshiyuki

AU - Doi, Keiko

AU - Tanaka, Yoko

AU - Fujimoto, Takahiro

AU - Machida, Takashi

AU - Ota, Takeharu

AU - Koyanagi, Midori

AU - Takashima, Yasuo

AU - Sasazuki, Takehiko

AU - Kuroki, Masahide

AU - Iwasaki, Akinori

AU - Shirasawa, Senji

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

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

Abstract

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