High-throughput molecular profiling of a P-cadherin overexpressing breast cancer model reveals new targets for the anti-cancer bacterial protein azurin.

Abstract

Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells. We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression levels. Azurin up-regulated apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. In the contrary, in invasive MCF-7/AZ.Pcad cells, azurin decreased the expression of genes associated with cell surface receptors and signal transduction, as well as biological adhesion. Further, azurin decreased adhesion of cells to proteins from the extracellular matrix (ECM) and altered protein expression of integrins α6, β4 and β1 and interfered with the ability of these cells to form mammospheres. Altogether, our results further enlighten the anti-cancer effects mediated by azurin in P-cadherin overexpression breast cancer models.

• Authors: Nuno Bernardes, Ana Sofia Ribeiro, Sofia Abreu, André F Vieira, Laura Carreto, Manuel Santos, Raquel Seruca, Joana Paredes, Arsenio M Fialho
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 50 Pg. 1-9 (May 2014) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 24509127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cadherins
• Integrins
• TP53 protein, human
• Tumor Suppressor Protein p53
• Azurin

Topics

• Apoptosis (drug effects, genetics)
• Azurin (pharmacology)
• Biomarkers, Tumor (biosynthesis, genetics)
• Breast Neoplasms (drug therapy, genetics, metabolism, pathology)
• Cadherins (biosynthesis)
• Cell Adhesion (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• High-Throughput Screening Assays (methods)
• Humans
• Integrins (biosynthesis, genetics)
• MCF-7 Cells
• Oligonucleotide Array Sequence Analysis (methods)
• Pseudomonas aeruginosa (metabolism)
• Signal Transduction (drug effects)
• Transcriptome (drug effects)
• Tumor Suppressor Protein p53 (metabolism)