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The Korean Association of Immunobiologists (대한면역학회)
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The Cell Cycle Regulatory Effects of High Dose 5-fluorouracil on Breast Cancer Cell Line

유방암세포주에서 고농도 5-fluorouracil의 세포주기 조절효과

  • Jang, Joung Soon (Department of Internal Medicine and Gyeong Sang Institute of Health Science, Gyeong Sang National University College of Medicine) ;
  • Yang, Jung Ill (Department of Internal Medicine and Gyeong Sang Institute of Health Science, Gyeong Sang National University College of Medicine) ;
  • Chang, Seho (Department of Internal Medicine and Gyeong Sang Institute of Health Science, Gyeong Sang National University College of Medicine) ;
  • Lee, Won Sup (Department of Internal Medicine and Gyeong Sang Institute of Health Science, Gyeong Sang National University College of Medicine) ;
  • Lee, Jong Seok (Department of Internal Medicine and Gyeong Sang Institute of Health Science, Gyeong Sang National University College of Medicine) ;
  • Ahn, Myung-Ju (Department of Internal Medicine, Hanyang University College of Medicine) ;
  • Park, Byung-Kiu (National Cancer Center)
  • 장정순 (경상대학교 의과대학 내과학교실 및 건강과학연구소) ;
  • 양중일 (경상대학교 의과대학 내과학교실 및 건강과학연구소) ;
  • 장세호 (경상대학교 의과대학 내과학교실 및 건강과학연구소) ;
  • 이원섭 (경상대학교 의과대학 내과학교실 및 건강과학연구소) ;
  • 이종석 (경상대학교 의과대학 내과학교실 및 건강과학연구소) ;
  • 안명주 (한양대학교 의과대학 내과학교실) ;
  • 박병규 (국립암센터)
  • Published : 2002.03.31
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Abstract

Background: Chemotherapy with 5-fluorouracil (5-FU) has been one of the mainstay in breast cancer treatment. The effects of high dose 5-FU on cell cycle regulation were studied in breast caner cells. Methods: A breast cancer cell line MCF-7 was used. Protein expressions of G1/S cyclins, $p21^{Waf1/Cip1}$, cdk2, E2F1 and retinoblastoma were tested by western blot analysis. Immunoprecipitation and immune complex kinase assay were done for the assessment of E2F1/RB interacton and the activity of cdk2 respectively. Results: $p21^{Waf1/Cip1}$ expression was barely detectable in control cells. With addition of 5-FU level of $p21^{Waf1/Cip1}$ were induced and cyclin D3 level was decreased as cell growth decreases. In accordance with increased expression of $p21^{Waf1/Cip1}$, cyclin E-associated cdk2 kinase activity was reduced. Retinoblastoma protein (RB) became dephosphorylated and E2F-1 binding activity with RB was increased. Conclusion: In this situation of high concentration of 5-FU breast cancer cells tend to be G1/S cell cycle arrested. Overexpression of $p21^{Waf1/Cip1}$ and dephosphorylation of RB may mediate the effectss of 5-FU by inhibiting E2F-1 activity, which contributes to G1/S cell cycle arrest. These results could be an indicating landmark for further study of high dose chemotherapy with 5-FU.

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