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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Prostate apoptosis response 4 (PAR4) expression modulates WNT signaling pathways in MCF7 breast cancer cells: A possible mechanism underlying PAR4-mediated docetaxel chemosensitivity

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Author(s):
de Bessa Garcia, Simone Aparecida ; Pavanelli, Ana Carolina ; Cruz e Melo, Natalia ; Nagai, Maria Aparecida
Total Authors: 4
Document type: Journal article
Source: International Journal of Molecular Medicine; v. 39, n. 4, p. 809-818, APR 2017.
Web of Science Citations: 5
Abstract

Docetaxel is an effective drug for the treatment of metastatic breast cancer. However, the exact mechanisms and/or markers associated with chemosensitivity or resistance to docetaxel remain unclear. We previously showed that the expression of prostate apoptosis response 4 (PAR4) inhibits the growth of MCF7 breast cancer cells and increases their sensitivity to docetaxel. Using cDNA microarray analysis, we evaluated transcriptome changes in MCF7 cells expressing increased levels of PAR4 and control cells before and after docetaxel treatment. Some of the top gene networks generated from the differentially expressed genes were related to the wingless-type MMTV integration 1 (WNT) canonical (WNT/-catenin) and non-canonical (-catenin-independent) pathways. The Human WNT signaling pathway RT2 profiler PCR array was used to validate the effects of PAR4 on the expression pattern of genes involved in the WNT pathway. CACNAD2A3, GDF5 and IL6 were upregulated and NANOG was downregulated in the MCF7 breast cancer cells expressing increased levels of PAR4 after treatment with docetaxel, likely indicating inactivation of the WNT/-catenin pathway. Upregulation of FGF7, LEF1 and TWIST1 indicated activation of the WNT/-catenin pathway. Although preliminary, our findings could be of particular interest for understanding the action of PAR4 in chemosensitivity, particularly to increase the specificity and effectiveness of drug treatment and overcome resistance to chemotherapy. Further studies are needed to better understand the biological roles of PAR4 in the regulation of WNT pathways in breast cancer cells in response to docetaxel and other chemotherapeutic agents. (AU)

FAPESP's process: 13/07035-4 - Evaluation of the functional role of intracellular and extracellular expression of PAR-4 (prostate apoptosis response-4) in the tumorigenic process of the breast: implications for chemosensitivity and potential antitumor
Grantee:Maria Aparecida Nagai
Support type: Regular Research Grants