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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

Resistance to TRAIL enhanced cell invasiveness.A. Migration assay of 231 cells and 231T cells. C. Invasion assay of 231 and 231T cells. Cells that passed through the membrane were counted in 10 representative fields. Diagrams for migration (B) and invasion (D) were shown, respectively. Data was shown as mean ± SD. *P<0.05; **P<0.01.
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pone-0099067-g003: Resistance to TRAIL enhanced cell invasiveness.A. Migration assay of 231 cells and 231T cells. C. Invasion assay of 231 and 231T cells. Cells that passed through the membrane were counted in 10 representative fields. Diagrams for migration (B) and invasion (D) were shown, respectively. Data was shown as mean ± SD. *P<0.05; **P<0.01.

Mentions: The acquisition of EMT can enhance the abilities of migration and invasion of cancer cells. Hence the western blot results had shown that resistance to TRAIL could induce EMT, we then evaluated both migration and invasion abilities by Transwell assay. After counting under light microscope and statistical calculation, we found that 231T cells had enhanced capabilities of both migration and invasion comparing with 231 cells (p<0.01) (Figure 3).


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)

Resistance to TRAIL enhanced cell invasiveness.A. Migration assay of 231 cells and 231T cells. C. Invasion assay of 231 and 231T cells. Cells that passed through the membrane were counted in 10 representative fields. Diagrams for migration (B) and invasion (D) were shown, respectively. Data was shown as mean ± SD. *P<0.05; **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0099067-g003: Resistance to TRAIL enhanced cell invasiveness.A. Migration assay of 231 cells and 231T cells. C. Invasion assay of 231 and 231T cells. Cells that passed through the membrane were counted in 10 representative fields. Diagrams for migration (B) and invasion (D) were shown, respectively. Data was shown as mean ± SD. *P<0.05; **P<0.01.
Mentions: The acquisition of EMT can enhance the abilities of migration and invasion of cancer cells. Hence the western blot results had shown that resistance to TRAIL could induce EMT, we then evaluated both migration and invasion abilities by Transwell assay. After counting under light microscope and statistical calculation, we found that 231T cells had enhanced capabilities of both migration and invasion comparing with 231 cells (p<0.01) (Figure 3).

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