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PTEN plays an important role in thrombin-mediated lung cancer cell functions.

Xu Z, Zhu L, Yao M, Zhong G, Dong Q, Yu A - Biomed Res Int (2015)

Bottom Line: The results indicated that thrombin downregulates the PTEN expression level and that PTEN plays an important role in thrombin-mediated Glc-82 functions, including cell cycle progression, cell apoptosis, and cell migration.The PI3K/AKT signaling pathway and its related proteins, including p27 and S phase kinase associated protein 2 (Skp2), are involved in the effects induced by PTEN downregulation.PAR1 plays a role in thrombin-mediated reduction of PTEN expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China ; The First Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan 453100, China.

ABSTRACT
Thrombin and its membrane receptor, protease-activated receptor 1 (PAR1), have been reported to promote the development of lung cancer in vitro and in vivo. However, the intracellular molecular mechanism or signaling pathway that mediates the cytological effects after the thrombin-receptor interaction is poorly understood. Our previous study observed that the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was downregulated in thrombin-stimulated lung cancer. In this study, the role of PTEN in thrombin-mediated cell function and the corresponding cell signaling pathway were studied in lung cancer cell Glc-82. The results indicated that thrombin downregulates the PTEN expression level and that PTEN plays an important role in thrombin-mediated Glc-82 functions, including cell cycle progression, cell apoptosis, and cell migration. The PI3K/AKT signaling pathway and its related proteins, including p27 and S phase kinase associated protein 2 (Skp2), are involved in the effects induced by PTEN downregulation. PAR1 plays a role in thrombin-mediated reduction of PTEN expression. This study suggested that the PTEN/PI3K/AKT signaling pathway plays an important role in thrombin/PAR1-mediated lung cancer cell growth and migration.

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The role of PTEN in thrombin-mediated effects on Glc-82 cells. (a) The role of PTEN in thrombin-mediated promotion of Glc-82 cell cycle progression. Glc-82, Mock, and Glc-PTEN-shRNA cells were starved for 24 h in serum-free medium before treatment without or with thrombin (0.5 U/mL) for 12 h. The cell cycle was evaluated by flow cytometer analysis. (b) The role of PTEN in thrombin-mediated protection of Glc-82 cells from serum deprivation-induced apoptosis. Cells were starved for 48 h in serum-free RPMI 1640 medium. Thrombin (0.5 U/mL) was added and incubated for a further 96 h. The cells were then collected and analyzed on the flow cytometer within 1 h after staining. (c) The role of PTEN in thrombin-mediated promotion of Glc-82 cells migration. Cells were allowed to migrate for 20 h, cells in serum-free medium without or with thrombin (0.5 U/mL); then three different visual fields were randomly selected to count the cell number and calculate the average migration rate (*P < 0.05, **P < 0.01).
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fig4: The role of PTEN in thrombin-mediated effects on Glc-82 cells. (a) The role of PTEN in thrombin-mediated promotion of Glc-82 cell cycle progression. Glc-82, Mock, and Glc-PTEN-shRNA cells were starved for 24 h in serum-free medium before treatment without or with thrombin (0.5 U/mL) for 12 h. The cell cycle was evaluated by flow cytometer analysis. (b) The role of PTEN in thrombin-mediated protection of Glc-82 cells from serum deprivation-induced apoptosis. Cells were starved for 48 h in serum-free RPMI 1640 medium. Thrombin (0.5 U/mL) was added and incubated for a further 96 h. The cells were then collected and analyzed on the flow cytometer within 1 h after staining. (c) The role of PTEN in thrombin-mediated promotion of Glc-82 cells migration. Cells were allowed to migrate for 20 h, cells in serum-free medium without or with thrombin (0.5 U/mL); then three different visual fields were randomly selected to count the cell number and calculate the average migration rate (*P < 0.05, **P < 0.01).

Mentions: As shown in Figure 4(a), thrombin significantly increased the number of cells in S phase by 18.56% in Glc-82 and by 26.14% in the Mock group. Compared with Glc-82 and Mock group, the number of cells in S phase in Glc-PTEN-shRNA cells was markedly deceased by 20.05–24.23% after thrombin treatment. This indicated that the effect of thrombin on Glc-82 cell cycle may be, at least partly, dependent on PTEN.


PTEN plays an important role in thrombin-mediated lung cancer cell functions.

Xu Z, Zhu L, Yao M, Zhong G, Dong Q, Yu A - Biomed Res Int (2015)

The role of PTEN in thrombin-mediated effects on Glc-82 cells. (a) The role of PTEN in thrombin-mediated promotion of Glc-82 cell cycle progression. Glc-82, Mock, and Glc-PTEN-shRNA cells were starved for 24 h in serum-free medium before treatment without or with thrombin (0.5 U/mL) for 12 h. The cell cycle was evaluated by flow cytometer analysis. (b) The role of PTEN in thrombin-mediated protection of Glc-82 cells from serum deprivation-induced apoptosis. Cells were starved for 48 h in serum-free RPMI 1640 medium. Thrombin (0.5 U/mL) was added and incubated for a further 96 h. The cells were then collected and analyzed on the flow cytometer within 1 h after staining. (c) The role of PTEN in thrombin-mediated promotion of Glc-82 cells migration. Cells were allowed to migrate for 20 h, cells in serum-free medium without or with thrombin (0.5 U/mL); then three different visual fields were randomly selected to count the cell number and calculate the average migration rate (*P < 0.05, **P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4377361&req=5

fig4: The role of PTEN in thrombin-mediated effects on Glc-82 cells. (a) The role of PTEN in thrombin-mediated promotion of Glc-82 cell cycle progression. Glc-82, Mock, and Glc-PTEN-shRNA cells were starved for 24 h in serum-free medium before treatment without or with thrombin (0.5 U/mL) for 12 h. The cell cycle was evaluated by flow cytometer analysis. (b) The role of PTEN in thrombin-mediated protection of Glc-82 cells from serum deprivation-induced apoptosis. Cells were starved for 48 h in serum-free RPMI 1640 medium. Thrombin (0.5 U/mL) was added and incubated for a further 96 h. The cells were then collected and analyzed on the flow cytometer within 1 h after staining. (c) The role of PTEN in thrombin-mediated promotion of Glc-82 cells migration. Cells were allowed to migrate for 20 h, cells in serum-free medium without or with thrombin (0.5 U/mL); then three different visual fields were randomly selected to count the cell number and calculate the average migration rate (*P < 0.05, **P < 0.01).
Mentions: As shown in Figure 4(a), thrombin significantly increased the number of cells in S phase by 18.56% in Glc-82 and by 26.14% in the Mock group. Compared with Glc-82 and Mock group, the number of cells in S phase in Glc-PTEN-shRNA cells was markedly deceased by 20.05–24.23% after thrombin treatment. This indicated that the effect of thrombin on Glc-82 cell cycle may be, at least partly, dependent on PTEN.

Bottom Line: The results indicated that thrombin downregulates the PTEN expression level and that PTEN plays an important role in thrombin-mediated Glc-82 functions, including cell cycle progression, cell apoptosis, and cell migration.The PI3K/AKT signaling pathway and its related proteins, including p27 and S phase kinase associated protein 2 (Skp2), are involved in the effects induced by PTEN downregulation.PAR1 plays a role in thrombin-mediated reduction of PTEN expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China ; The First Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan 453100, China.

ABSTRACT
Thrombin and its membrane receptor, protease-activated receptor 1 (PAR1), have been reported to promote the development of lung cancer in vitro and in vivo. However, the intracellular molecular mechanism or signaling pathway that mediates the cytological effects after the thrombin-receptor interaction is poorly understood. Our previous study observed that the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was downregulated in thrombin-stimulated lung cancer. In this study, the role of PTEN in thrombin-mediated cell function and the corresponding cell signaling pathway were studied in lung cancer cell Glc-82. The results indicated that thrombin downregulates the PTEN expression level and that PTEN plays an important role in thrombin-mediated Glc-82 functions, including cell cycle progression, cell apoptosis, and cell migration. The PI3K/AKT signaling pathway and its related proteins, including p27 and S phase kinase associated protein 2 (Skp2), are involved in the effects induced by PTEN downregulation. PAR1 plays a role in thrombin-mediated reduction of PTEN expression. This study suggested that the PTEN/PI3K/AKT signaling pathway plays an important role in thrombin/PAR1-mediated lung cancer cell growth and migration.

Show MeSH
Related in: MedlinePlus