Immune Netw.  2002 Mar;2(1):60-64. 10.4110/in.2002.2.1.60.

The Cell Cycle Regulatory Effects of High Dose 5-fluorouracil on Breast Cancer Cell Line

• Jang JS
• Yang JI
• Chang SH
• Lee WS
• Lee JS
• Ahn MJ
• Park BK

• KMID: 1571394
• DOI: http://doi.org/10.4110/in.2002.2.1.60

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.

Keyword

5-FU; breast cancer; cell cycle regulation

MeSH Terms

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
Antigen-Antibody Complex
Cyclin D3
Cyclins
Fluorouracil
Phosphotransferases
Retinoblastoma Protein