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Trail resistance induces epithelial-mesenchymal transition and enhances invasiveness by suppressing PTEN via miR-221 in breast cancer.

Wang H, Xu C, Kong X, Li X, Kong X, Wang Y, Ding X, Yang Q - PLoS ONE (2014)

Bottom Line: In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line.We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness.Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.

ABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis of cancer cells and is verified effective to various cancers. However, a variety of breast cancer cell lines are resistant to TRAIL and the mechanisms of resistance are largely unknown. In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line. We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness. We further demonstrated PTEN was down-regulated in TRAIL-resistant cells. Silencing miR-221, PTEN expression was up-regulated, the process of EMT could be reversed, and the ability of migration and invasion were correspondingly weakened. We also demonstrated knockdown of miR-221 could reverse resistance to TRAIL partially by targeting PTEN. Our findings suggest that resistance to TRAIL could induce EMT and enhance invasiveness by suppressing PTEN via miR-221. Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

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Related in: MedlinePlus

TRAIL-resistant cells (231T) were resistant to TRAIL and had different morphology from MDA-MB-231 cells (231).A. Sensitization of 231 cells and 231T cells to TRAIL at gradient concentrations was measured by MTT assay. Points represented the average of three independent experiments. Bars stood for SD; *P<0.05; **P<0.01; B and C. Resistance to TRAIL induced morphological change. B: 231 cells. C: 231T cells. Cells were observed under a light microscope.
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pone-0099067-g001: TRAIL-resistant cells (231T) were resistant to TRAIL and had different morphology from MDA-MB-231 cells (231).A. Sensitization of 231 cells and 231T cells to TRAIL at gradient concentrations was measured by MTT assay. Points represented the average of three independent experiments. Bars stood for SD; *P<0.05; **P<0.01; B and C. Resistance to TRAIL induced morphological change. B: 231 cells. C: 231T cells. Cells were observed under a light microscope.

Mentions: We successfully established the TRAIL-resistant MDA-MB-231 cells (231T) as described above. They were obviously resistant to rhTRAIL comparing with parental MDA-MB-231 (231) by MTT assay (Figure 1A). Furthermore, the morphology of 231T cells was different with 231 cells under a light microscope. They became longer and richer than 231 cells, and emerged a cluster growth, just like the ear of wheat (Figure 1B and C).


Trail resistance induces epithelial-mesenchymal transition and enhances invasiveness by suppressing PTEN via miR-221 in breast cancer.

Wang H, Xu C, Kong X, Li X, Kong X, Wang Y, Ding X, Yang Q - PLoS ONE (2014)

TRAIL-resistant cells (231T) were resistant to TRAIL and had different morphology from MDA-MB-231 cells (231).A. Sensitization of 231 cells and 231T cells to TRAIL at gradient concentrations was measured by MTT assay. Points represented the average of three independent experiments. Bars stood for SD; *P<0.05; **P<0.01; B and C. Resistance to TRAIL induced morphological change. B: 231 cells. C: 231T cells. Cells were observed under a light microscope.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4048247&req=5

pone-0099067-g001: TRAIL-resistant cells (231T) were resistant to TRAIL and had different morphology from MDA-MB-231 cells (231).A. Sensitization of 231 cells and 231T cells to TRAIL at gradient concentrations was measured by MTT assay. Points represented the average of three independent experiments. Bars stood for SD; *P<0.05; **P<0.01; B and C. Resistance to TRAIL induced morphological change. B: 231 cells. C: 231T cells. Cells were observed under a light microscope.
Mentions: We successfully established the TRAIL-resistant MDA-MB-231 cells (231T) as described above. They were obviously resistant to rhTRAIL comparing with parental MDA-MB-231 (231) by MTT assay (Figure 1A). Furthermore, the morphology of 231T cells was different with 231 cells under a light microscope. They became longer and richer than 231 cells, and emerged a cluster growth, just like the ear of wheat (Figure 1B and C).

Bottom Line: In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line.We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness.Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.

ABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis of cancer cells and is verified effective to various cancers. However, a variety of breast cancer cell lines are resistant to TRAIL and the mechanisms of resistance are largely unknown. In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line. We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness. We further demonstrated PTEN was down-regulated in TRAIL-resistant cells. Silencing miR-221, PTEN expression was up-regulated, the process of EMT could be reversed, and the ability of migration and invasion were correspondingly weakened. We also demonstrated knockdown of miR-221 could reverse resistance to TRAIL partially by targeting PTEN. Our findings suggest that resistance to TRAIL could induce EMT and enhance invasiveness by suppressing PTEN via miR-221. Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

Show MeSH
Related in: MedlinePlus