The Cell Cycle Regulatory Effects of High Dose 5-fluorouracil on Breast Cancer Cell Line.
- Author:
Joung Soon JANG
1
;
Jung Ill YANG
;
Se Ho CHANG
;
Won Sup LEE
;
Jong Seok LEE
;
Myung Ju AHN
;
Byung Kiu PARK
Author Information
- Publication Type:Original Article
- Keywords: 5-FU; breast cancer; cell cycle regulation
- MeSH: Antigen-Antibody Complex; Blotting, Western; Breast Neoplasms*; Breast*; Cell Cycle Checkpoints; Cell Cycle*; Cell Line*; Cyclin D3; Cyclins; Drug Therapy; Fluorouracil*; Immunoprecipitation; Phosphotransferases; Retinoblastoma; Retinoblastoma Protein
- From:Immune Network 2002;2(1):60-64
- CountryRepublic of Korea
- Language:Korean
- 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.
