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Jang, Yang, Chang, Lee, Lee, Ahn, and Park: The Cell Cycle Regulatory Effects of High Dose 5-fluorouracil on Breast Cancer Cell Line
Original Article

Immune Network 2002; 2(1): 60-64.

Published online: 31 March 2002

DOI: https://doi.org/10.4110/in.2002.2.1.60

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

Joung Soon Jang1, Jung Ill Yang1, Se Ho Chang1, Won Sup Lee1, Jong Seok Lee1, Myung Ju Ahn2, Byung Kiu Park3

1Department of Internal Medicine and Gyeong Sang Institute of Health Science, Gyeong Sang National University College of Medicine, Korea.

2Department of Internal Medicine, Hanyang University College of Medicine, Korea.

3National Cancer Center, Korea.

Corresponding Author (jsjang@nongae.gsnu.ac.kr)

Copyright © 2002 The Korean Association of Immunologists

(open-access):

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

BACKGROUND/AIMS

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, p21Waf1/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

p21Waf1/Cip1 expression was barely detectable in control cells. With addition of 5-FU level of p21Waf1/Cip1 were induced and cyclin D3 level was decreased as cell growth decreases. In accordance with increased expression of p21Waf1/Cip1, cyclin E-associated cdk2 kinase activity was reduced. Retinoblastoma protein (RB) became dephosphorylated and E2F-1 binding activity with RB was increased.

CONCLUSIONS

In this situation of high concentration of 5-FU breast cancer cells tend to be G1/S cell cycle arrested. Overexpression of p21Waf1/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.

Keywords: 5-FU, breast cancer, cell cycle regulation

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