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Serum deprivation response inhibits breast cancer progression by blocking transforming growth factor-β signaling.

Tian Y, Yu Y, Hou LK, Chi JR, Mao JF, Xia L, Wang X, Wang P, Cao XC - Cancer Sci. (2016)

Bottom Line: Here, we found that SDPR is downregulated in human breast cancer.In conclusion, our results showed that SDPR inhibits breast cancer progression by blocking TGF-β signaling.SDPR depletion induces epithelial-mesenchymal transition by activation of TGF-β signaling.

View Article: PubMed Central - PubMed

Affiliation: The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.

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Transforming growth factor‐β (TGF‐β) restores the serum deprivation response (SDPR)‐induced MET phenotype. (a) Cellular morphology of the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β1 treatment. (b) RT‐qPCR analysis of mRNA expression of the mesenchymal markers Vimentin and N‐cadherin (CDH2), and epithelial markers E‐cadherin (CDH1) and β‐catenin (CTNNB1) in the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β1 treatment. (c) Western blot analysis of protein expression of the mesenchymal markers Vimentin and N‐cadherin, and epithelial markers E‐cadherin and β‐catenin in the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β treatment.
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cas12879-fig-0006: Transforming growth factor‐β (TGF‐β) restores the serum deprivation response (SDPR)‐induced MET phenotype. (a) Cellular morphology of the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β1 treatment. (b) RT‐qPCR analysis of mRNA expression of the mesenchymal markers Vimentin and N‐cadherin (CDH2), and epithelial markers E‐cadherin (CDH1) and β‐catenin (CTNNB1) in the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β1 treatment. (c) Western blot analysis of protein expression of the mesenchymal markers Vimentin and N‐cadherin, and epithelial markers E‐cadherin and β‐catenin in the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β treatment.

Mentions: Transforming growth factor‐β (TGF‐β) is a pleiotropic cytokine which contributes to wound healing, angiogenesis, fibrosis and cancer.12 We observed that the ability of cell proliferation and invasion was reduced after treatment with TGF‐β inhibitor SB431542 (Fig. S1a–d). Furthermore, SB431542 could inhibit the EMT‐like phenotype in MDA‐MB‐231 cells (Fig. S1e). To investigate whether TGF‐β plays an important role in the function of SDPR, we performed a luciferase assay to determine the effect of SDPR on the TGF‐β signaling activity. As shown in Figure 5(a), the luciferase activity was significantly increased in SDPR‐depleted MCF10A cells (Fig. 5a). The TGF‐β1 expression was also elevated in SDPR‐depleted MCF10A cells by ELISA assay (Fig. 5b). The immunofluorescence staining analysis showed that Smad2/3 translocated into the nucleus in SDPR‐depleted MCF10A cells more than in the control cells (Fig. 5c). Furthermore, the expression of phosphorylated Smad2/3 were greatly increased in SDPR‐depleted cells by western blot (Fig. 5d). The number of proliferating cells was much lower in SDPR‐depleted cells after treatment with TGF‐β inhibitor SB‐431542 (Fig. 5e). Furthermore, the malignant phenotype induced by SDPR depletion was reversed by treatment with TGF‐β inhibitor SB‐431542 (Fig. 5f–h). We also observed that the percentage of cells at S phase was dramatically decreased in SDPR‐depleted MCF10A cells after treatment with SB431542 (Fig. 6i). Furthermore, the expression of p21 was elevated, while the expression of Cyclin D1 was decreased after treatment with SB431542 (Fig. 6j).


Serum deprivation response inhibits breast cancer progression by blocking transforming growth factor-β signaling.

Tian Y, Yu Y, Hou LK, Chi JR, Mao JF, Xia L, Wang X, Wang P, Cao XC - Cancer Sci. (2016)

Transforming growth factor‐β (TGF‐β) restores the serum deprivation response (SDPR)‐induced MET phenotype. (a) Cellular morphology of the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β1 treatment. (b) RT‐qPCR analysis of mRNA expression of the mesenchymal markers Vimentin and N‐cadherin (CDH2), and epithelial markers E‐cadherin (CDH1) and β‐catenin (CTNNB1) in the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β1 treatment. (c) Western blot analysis of protein expression of the mesenchymal markers Vimentin and N‐cadherin, and epithelial markers E‐cadherin and β‐catenin in the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β treatment.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814251&req=5

cas12879-fig-0006: Transforming growth factor‐β (TGF‐β) restores the serum deprivation response (SDPR)‐induced MET phenotype. (a) Cellular morphology of the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β1 treatment. (b) RT‐qPCR analysis of mRNA expression of the mesenchymal markers Vimentin and N‐cadherin (CDH2), and epithelial markers E‐cadherin (CDH1) and β‐catenin (CTNNB1) in the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β1 treatment. (c) Western blot analysis of protein expression of the mesenchymal markers Vimentin and N‐cadherin, and epithelial markers E‐cadherin and β‐catenin in the SDPR‐overexpressed MDA‐MB‐231 with or without TGF‐β treatment.
Mentions: Transforming growth factor‐β (TGF‐β) is a pleiotropic cytokine which contributes to wound healing, angiogenesis, fibrosis and cancer.12 We observed that the ability of cell proliferation and invasion was reduced after treatment with TGF‐β inhibitor SB431542 (Fig. S1a–d). Furthermore, SB431542 could inhibit the EMT‐like phenotype in MDA‐MB‐231 cells (Fig. S1e). To investigate whether TGF‐β plays an important role in the function of SDPR, we performed a luciferase assay to determine the effect of SDPR on the TGF‐β signaling activity. As shown in Figure 5(a), the luciferase activity was significantly increased in SDPR‐depleted MCF10A cells (Fig. 5a). The TGF‐β1 expression was also elevated in SDPR‐depleted MCF10A cells by ELISA assay (Fig. 5b). The immunofluorescence staining analysis showed that Smad2/3 translocated into the nucleus in SDPR‐depleted MCF10A cells more than in the control cells (Fig. 5c). Furthermore, the expression of phosphorylated Smad2/3 were greatly increased in SDPR‐depleted cells by western blot (Fig. 5d). The number of proliferating cells was much lower in SDPR‐depleted cells after treatment with TGF‐β inhibitor SB‐431542 (Fig. 5e). Furthermore, the malignant phenotype induced by SDPR depletion was reversed by treatment with TGF‐β inhibitor SB‐431542 (Fig. 5f–h). We also observed that the percentage of cells at S phase was dramatically decreased in SDPR‐depleted MCF10A cells after treatment with SB431542 (Fig. 6i). Furthermore, the expression of p21 was elevated, while the expression of Cyclin D1 was decreased after treatment with SB431542 (Fig. 6j).

Bottom Line: Here, we found that SDPR is downregulated in human breast cancer.In conclusion, our results showed that SDPR inhibits breast cancer progression by blocking TGF-β signaling.SDPR depletion induces epithelial-mesenchymal transition by activation of TGF-β signaling.

View Article: PubMed Central - PubMed

Affiliation: The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.

Show MeSH
Related in: MedlinePlus