Clusterin: A potential target for improving response to antiestrogens

  • Authors:
    • Sara Toffanin
    • Maria Grazia Daidone
    • Patrizia Miodini
    • Loris De Cecco
    • Paolo Gandellini
    • Vera Cappelletti
  • View Affiliations

  • Published online on: Wednesday, October 1, 2008
  • Pages: 791-798
  • DOI: 10.3892/ijo_00000066

Abstract

Antiestrogens represent the first line of therapy in the treatment of estrogen receptor-positive (ER+) breast cancer patients. Unfortunately, up to 40% of patients develop resistance associated with progression and frequently die for metastatic breast cancer. The molecular events leading to pharmacological resistance are not completely understood. We attempted to verify in an experimental model the role of cytoplasmic clusterin (CLU), a cytoprotective protein found to be up-regulated in antiestrogen-resistant patients, following neoadjuvant treatment with toremifene. The role of cytoplasmic clusterin in modulating response to two antiestrogens (toremifene and tamoxifen) was studied in two ER+ anti-estrogen-sensitive cell lines (MCF-7, 734B) and one ER+ antiestrogen-resistant cell line (T47D) using siRNA strategy. Resistant cells were characterised by higher levels of cytoplasmic clusterin than sensitive cells, and antiestrogen treatments up-regulated clusterin levels in both sensitive and resistant cell lines. Treatment with siRNA completely abolished cytoplasmic clusterin expression in all cell lines, but its down-regulation resulted in a significant decrease of cell growth only in the resistant line. We therefore concluded that: i) basal clusterin levels are higher in antiestrogen resistant cells, ii) clusterin is up-regulated following antiestrogen treatment independently of the sensitivity of the cell line, iii) down-regulation of cytoplasmic clusterin restores sensitivity to toremifene in the antiestrogen-resistant cell line. Such results support the concept that targeting CLU could represent a promising therapeutic strategy in association with antiestrogen treatment in breast cancer patients.
Journal Cover

October 2008
Volume 33 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Toffanin, S., Daidone, M., Miodini, P., De Cecco, L., Gandellini, P., & Cappelletti, V. (2008). Clusterin: A potential target for improving response to antiestrogens. International Journal of Oncology, 33(4), 791-798.
MLA
Toffanin, Daidone, Miodini, De Cecco, Gandellini, and Vera Cappelletti. "Clusterin: A potential target for improving response to antiestrogens." International Journal of Oncology International Journal of Oncology 33.4 (2008): 791-798.
Chicago
Toffanin, Daidone, Miodini, De Cecco, Gandellini, and Vera Cappelletti. "Clusterin: A potential target for improving response to antiestrogens." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 791-798.