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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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Resistance to TRAIL induced EMT.A.The mesenchymal markers, including N-cad, fibronectin, vimentin, and Snail were examined by western blot analysis. β-actin was used to confirm equal loading of samples. B. The mRNA expressions of transcriptional factors including Snail, Twist1, Zeb2, Foxq1 and FoxC2. *P<0.05; **P<0.01.
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pone-0099067-g002: Resistance to TRAIL induced EMT.A.The mesenchymal markers, including N-cad, fibronectin, vimentin, and Snail were examined by western blot analysis. β-actin was used to confirm equal loading of samples. B. The mRNA expressions of transcriptional factors including Snail, Twist1, Zeb2, Foxq1 and FoxC2. *P<0.05; **P<0.01.

Mentions: Once EMT is familiar with chemotherapeutics-resistance cancer cells, combining with the morphological transformation and documents, we hypothesized that in 231T cells, EMT also existed. So we then examined the EMT markers in 231 cells and 231T cells by western blot. Because in MDA-MB-231 cells, the expression of E-cadherin and other epithelial markers are very low, almost undetectable, we examined some mesenchymal markers whose elevation also could indicate the occurrence of EMT. The results showed that the mesenchymal markers, including N-cadherin, fibronectin and vimentin, were all over-expressed in 231T cells. Moreover, the expression of Snail, a transcriptional repressor of E-cadherin, was also arose (Figure 2A). The mRNA levels of some transcription factors were also examined by real-time PCR (Figure 2B). The results showed that Snail and Twist were up-regulated in 231T cells, and other factors were almost no change. These results verified that resistance to TRAIL could induce EMT.


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 induced EMT.A.The mesenchymal markers, including N-cad, fibronectin, vimentin, and Snail were examined by western blot analysis. β-actin was used to confirm equal loading of samples. B. The mRNA expressions of transcriptional factors including Snail, Twist1, Zeb2, Foxq1 and FoxC2. *P<0.05; **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0099067-g002: Resistance to TRAIL induced EMT.A.The mesenchymal markers, including N-cad, fibronectin, vimentin, and Snail were examined by western blot analysis. β-actin was used to confirm equal loading of samples. B. The mRNA expressions of transcriptional factors including Snail, Twist1, Zeb2, Foxq1 and FoxC2. *P<0.05; **P<0.01.
Mentions: Once EMT is familiar with chemotherapeutics-resistance cancer cells, combining with the morphological transformation and documents, we hypothesized that in 231T cells, EMT also existed. So we then examined the EMT markers in 231 cells and 231T cells by western blot. Because in MDA-MB-231 cells, the expression of E-cadherin and other epithelial markers are very low, almost undetectable, we examined some mesenchymal markers whose elevation also could indicate the occurrence of EMT. The results showed that the mesenchymal markers, including N-cadherin, fibronectin and vimentin, were all over-expressed in 231T cells. Moreover, the expression of Snail, a transcriptional repressor of E-cadherin, was also arose (Figure 2A). The mRNA levels of some transcription factors were also examined by real-time PCR (Figure 2B). The results showed that Snail and Twist were up-regulated in 231T cells, and other factors were almost no change. These results verified that resistance to TRAIL could induce EMT.

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