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Myosin light chain kinase is responsible for high proliferative ability of breast cancer cells via anti-apoptosis involving p38 pathway.

Abstract：

AIM:To investigate whether myosin light chain kinase (MLCK) contributed to the high proliferative ability of breast cancer cells. METHODS:Soft agar colony formation on the MCF-7 and LM-MCF-7 cell lines was determined. The cell cycles of MCF-7 and LM-MCF-7 were detected using flow cytometry analysis. Western blot analysis was performed to detect the expression levels of p-ERK1/2, total-ERK1/2, p-p38, total p38, p-JNK, total-JNK, survivin, Bcl-2, p-MLC, caspase-9, cleaved caspase-9, and MLCK. After treatment with adriamycin (ADR), ML-7 and SB203580, apoptosis was examined using flow cytometry analysis and Annexin V-FITC fluorescence microscopy. RESULTS:The breast cancer LM-MCF-7 cell line with high metastasis potential (a metastitic sub-clone of MCF-7) had higher anti-apoptosis ability relative to MCF-7 cells in response to adriamycin treatment (apoptosis rate: 6.76% vs 28.58%, P<0.05). Moreover, the expression level of MLCK was upregulated and the level of phosphorylated p38 (p-p38) was decreased in LM-MCF-7 cells. Flow cytometry analysis showed that ML-7, selective inhibitor of MLCK, could induce apoptosis of the LM-MCF-7 cells, in which the level of p-p38 was increased. Meanwhile, the expression levels of Bcl-2 and survivin were downregulated, while the caspase-9 was upregulated suggesting that the cells were undergone apoptosis. Flow cytometry analysis showed that SB203580, an inhibitor of p38, abolished ML-7-induced apoptosis, which resulted in the upregulation of Bcl-2 and survivin, and downregulation of caspase-9, suggesting that Bcl-2, survivin and caspase-9 are downstream effectors of p38. CONCLUSION:MLCK is responsible for high proliferative ability of breast cancer cells through anti-apoptosis, in which p38 pathway was involved.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Cui WJ,Liu Y,Zhou XL,Wang FZ,Zhang XD,Ye LH

doi

10.1038/aps.2010.56

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

725-32

issue

eissn

1671-4083

issn

1745-7254

pii

aps201056

journal_volume

pub_type

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Myosin light chain kinase is responsible for high proliferative ability of breast cancer cells via anti-apoptosis involving p38 pathway.