Stable knockdown of clusterin by vectorbased RNA interference in a human breast cancer cell line inhibits tumour cell invasion and metastasis

Author(s): Li J, Jia L, Zhao P, Jiang Y, Zhong S, et al.


Objective: Overexpression of the clusterin (CLU) gene occurs in breast cancer and is associated with lymph node metastasis. The present study explored the effect of CLU silencing on invasion and metastasis, and the relationship between CLU expression and the extracellular signal-regulated kinase (ERK) / matrix metalloproteinase-9 (MMP) signalling pathway in human breast cancer cells.

Methods: A pcDNA3.1-based RNA interference approach was used to knockdown the CLU gene in MDA-231 cells (MDA-231-CLUi); control MDA-231 cells were transfected with an empty vector (MDA-231-Vec). Reverse transcription-polymerase chain reaction was used to assess CLU and MMP-9 mRNA levels, and Western blotting was used to analyse CLU, MMP-9 and ERK protein levels. Metastatic potential was evaluated using in vitro and in vivo models of invasion and metastasis.

Results: Compared with MDA-231-Vec cells, the MDA-231-CLUi cells demonstrated reduced migration and invasion in vitro and decreased metastatic potential in vivo. Reintroduction and reexpression of the CLU gene into the MDA-231-CLUi cells restored the invasive phenotype. MMP-9 mRNA and protein levels were reduced in MDA-231-CLUi cells, and there was a correlation between activated ERK and CLU and MMP-9 protein levels.

Conclusion: CLU may regulate the aggressive behaviour of human breast cancer cells through modulation of ERK signalling and MMP9 expression.

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