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International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Article

P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells

  • Authors:
    • So Young Eun
    • Young Shin Ko
    • Sang Won Park
    • Ki Churl Chang
    • Hye Jung Kim
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-751, Republic of Korea
  • Pages: 195-202
    |
    Published online on: May 11, 2015
       https://doi.org/10.3892/or.2015.3972
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Abstract

Tumor metastasis is considered the main cause of mortality in cancer patients, thus it is important to investigate the differences between high- and low-metastatic cancer cells. Our previous study showed that the highly metastatic breast cancer cell line MDA-MB-231 released higher levels of ATP and exhibited higher P2Y2R activity compared with the low‑metastatic breast cancer cell line MCF-7. In addition, P2Y2R activation by ATP released from MDA-MB-231 cells induced hypoxia-inducible factor-1α expression, lysyl oxidase secretion and collagen crosslinking, generating a receptive microenvironment for pre-metastatic niche formation. Thus, in the present study, we investigated which P2Y2R-related signaling pathways are involved in the invasion of breast cancer cells. The highly metastatic breast cancer cells MDA-MB-231 and SK-BR-3 showed higher invasion than MCF-7 and T47D cells at a basal level, which was abolished through P2Y2R knockdown or in the presence of apyrase, an enzyme that hydrolyzes extracellular nucleotides. MDA-MB‑231 cells also showed high levels of mesenchymal markers, such as Snail, Vimentin and N-cadherin, but not the epithelial marker E-cadherin and this expression was inhibited through ATP degradation or P2Y2R knockdown. Moreover, SK-BR-3 and MDA-MB231 cells exhibited higher ERK and PKC phosphorylation levels than T47D and MCF-7 cells and upregulated phospho-ERK and -PKC levels in MDA-MB-231 cells were significantly downregulated by apyrase or P2Y2R knockdown. Specific inhibitors of ERK, PKC and PLC markedly reduced the invasion and levels of mesenchymal marker expression in MDA-MB-231 cells. These results suggest that over-activated ERK and PKC pathways are involved in the P2Y2R-mediated invasion of breast cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Eun SY, Ko YS, Park SW, Chang KC and Kim HJ: P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells. Oncol Rep 34: 195-202, 2015.
APA
Eun, S.Y., Ko, Y.S., Park, S.W., Chang, K.C., & Kim, H.J. (2015). P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells. Oncology Reports, 34, 195-202. https://doi.org/10.3892/or.2015.3972
MLA
Eun, S. Y., Ko, Y. S., Park, S. W., Chang, K. C., Kim, H. J."P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells". Oncology Reports 34.1 (2015): 195-202.
Chicago
Eun, S. Y., Ko, Y. S., Park, S. W., Chang, K. C., Kim, H. J."P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells". Oncology Reports 34, no. 1 (2015): 195-202. https://doi.org/10.3892/or.2015.3972
Copy and paste a formatted citation
x
Spandidos Publications style
Eun SY, Ko YS, Park SW, Chang KC and Kim HJ: P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells. Oncol Rep 34: 195-202, 2015.
APA
Eun, S.Y., Ko, Y.S., Park, S.W., Chang, K.C., & Kim, H.J. (2015). P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells. Oncology Reports, 34, 195-202. https://doi.org/10.3892/or.2015.3972
MLA
Eun, S. Y., Ko, Y. S., Park, S. W., Chang, K. C., Kim, H. J."P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells". Oncology Reports 34.1 (2015): 195-202.
Chicago
Eun, S. Y., Ko, Y. S., Park, S. W., Chang, K. C., Kim, H. J."P2Y2 nucleotide receptor-mediated extracellular signal-regulated kinases and protein kinase C activation induces the invasion of highly metastatic breast cancer cells". Oncology Reports 34, no. 1 (2015): 195-202. https://doi.org/10.3892/or.2015.3972
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