Secretory clusterin (sCLU) overexpression is associated with resistance to preoperative neoadjuvant chemotherapy in primary breast cancer

Author(s): Niu ZH, Wang Y, Chun B, Li CX, Wu L


Objectives: Preoperative chemotherapy is often used in patients with locally advanced breast cancer. However, commonly used clinical and pathological parameters are poor predictors of response to this type of therapy. The secreted form of the CLU protein (sCLU) is a glycosylated protein of 76-80 kDa. It has become increasingly clear that in most cells sCLU is a stress-associated cytoprotective protein that is upregulated by various apoptotic triggers. Furthermore, sCLU confers resistance by some unknown mechanism when overexpressed. The purpose of the present study was to examine the sCLU proteins as predictors of clinical outcome and response to chemotherapy in locally advanced breast cancer.

Patients and methods: The expression levels of sCLU was determined by immunohistochemistry before preoperative chemotherapy in 72 patients with locally advanced breast cancer. All patients were treated with cyclophosphamide/doxorubicin/5-FU(CAF) and some patients received additional treatment with docetaxel. Expression data were compared with patients' clinical and pathological features, clinical outcome, and response to chemotherapy.

Results: The results showed sCLU expression before preoperative chemotherapy was inversely related to the tumor size, expression of estrogen and progesterone receptors. High preoperative expression of sCLU was associated with resistance to CAF therapy, but not with resistance to docetaxel.

Conclusions: We, therefore, suggested sCLU expression may be a useful marker for predicting response to preoperative chemotherapy and clinical outcome in patients with locally advanced breast cancer.

Similar Articles

Current management of small cell lung cancer

Author(s): Neal JW, Gubens MA, Wakelee HA

Mechanisms of resistance to cisplatin

Author(s): Kartalou M, Essigmann JM

Expression of clusterin in human pancreatic cancer

Author(s): Xie MJ, Motoo Y, Su SB, Mouri H, Ohtsubo K, et al.

Clusterin interacts with Paclitaxel and confer Paclitaxel resistance in ovarian cancer

Author(s): Park DC, Yeo SG, Wilson MR, Yerbury JJ, Kwong J, et al.

Regulation of chemosensitivity and migration by clusterin in non-small cell lung cancer cells

Author(s): Cheng CY, Cherng SH, Wu WJ, Yang TY, Huang XY, et al.

Clusterin as a therapeutic target for radiation sensitization in a lung cancer model

Author(s): Cao C, Shinohara ET, Li H, Niermann KJ, Kim KW, et al.

Deguelin, A PI3K/AKT inhibitor, enhances chemosensitivity of leukaemia cells with an active PI3K/AKT pathway

Author(s): Bortul R, Tazzari PL, Billi AM, Tabellini G, Mantovani I, et al.

Modulation of PI3K/Akt pathway by E1a mediates sensitivity to cisplatin

Author(s): Guinea Viniegra J, Hernández Losa J, Sánchez-Arévalo VJ, ParadaCobo C, FernándezSoria VM, et al.

Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance

Author(s): McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F, et al.

Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance

Author(s): McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, et al.

Raf kinase as a target for anticancer therapeutics

Author(s): Sridhar SS, Hedley D, Siu LL

Mechanisms controlling sensitivity to platinum complexes: role of p53 and DNA mismatch repair

Author(s): Manic S, Gatti L, Carenini N, Fumagalli G, Zunino F, et al.

Clusterin regulates drug-resistance in melanoma cells

Author(s): Hoeller C, Pratscher B, Thallinger C, Winter D, Fink D, et al.

The Raf/MEK/ERK pathway: new concepts of activation

Author(s): Peyssonnaux C, Eychène A