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Overexpression of matrix metalloproteinase-9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling.


ABSTRACT:

Objectives

Matrix metalloproteinase 9 (MMP-9) has been frequently noticed in the breast cancers. In this study, we aim to investigate the associations of MMP-9 with the activation of transforming growth factor beta (TGF-?)/SMAD signalling and the malignancy of breast malignant tumour cells.

Materials and methods

The distributions of MMP-9 and TGF-? in the tissues of canine breast cancers were screened by immunohistochemical assays. A recombinant plasmid expressing mouse MMP-9 was generated and transiently transfected into three different breast cancer cell lines. Cell Counting Kit-8 and colony formation assay were used to study cell viability. Migration and invasion ability were analysed by wound assay and transwell filters. Western blot and quantitative real-time PCR were used to determine the protein and mRNA expression.

Result

Remarkable strong MMP-9 and TGF-? signals were observed in the malignant tissues of canine breast cancers. In the cultured three cell lines receiving recombinant plasmid expressing mouse MMP-9, the cell malignancy was markedly increased, including the cell colony formation, migration and epithelial-mesenchymal transition. The levels of activated TGF-?, as well as SMAD4, SMAD2/3 and phosphorylation of SMAD2, were increased, reflecting an activation of TGF-?/SMAD signalling. We also demonstrated that the inhibitors specific for MMP-9 and TGF-? sufficiently blocked the overexpressing MMP-9 induced the activation of SMAD signalling and enhancement on invasion in the tested breast cancer cell lines.

Conclusion

Overexpression of MMP-9 increases the malignancy of breast cancer cell lines, largely via activation of the TGF-?/SMAD signalling.

SUBMITTER: Dong H 

PROVIDER: S-EPMC6797518 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Overexpression of matrix metalloproteinase-9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling.

Dong Haodi H   Diao Hongxiu H   Zhao Ying Y   Xu Huihao H   Pei Shimin S   Gao Jiafeng J   Wang Jie J   Hussain Tariq T   Zhao Deming D   Zhou Xiangmei X   Lin Degui D  

Cell proliferation 20190702 5


<h4>Objectives</h4>Matrix metalloproteinase 9 (MMP-9) has been frequently noticed in the breast cancers. In this study, we aim to investigate the associations of MMP-9 with the activation of transforming growth factor beta (TGF-β)/SMAD signalling and the malignancy of breast malignant tumour cells.<h4>Materials and methods</h4>The distributions of MMP-9 and TGF-β in the tissues of canine breast cancers were screened by immunohistochemical assays. A recombinant plasmid expressing mouse MMP-9 was  ...[more]

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