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Potassium channel ether à go-go1 is aberrantly expressed in human liposarcoma and promotes tumorigenesis.

Wu J, Zhong D, Wei Y, Wu X, Kang L, Ding Z - Biomed Res Int (2014)

Bottom Line: The ether à go-go1 (Eag1) channel is overexpressed in a variety of cancers.Then, the protein expression of Eag1 in 131 different adipose tissues from 109 patients was detected by immunohistochemistry.It was found that Eag1 was aberrantly expressed in over 67% liposarcomas, with a higher frequency than in lipoma, hyperplasia, inflammation, and normal adipose tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhanghua Road 269, Zhangzhou 363000, China.

ABSTRACT
The ether à go-go1 (Eag1) channel is overexpressed in a variety of cancers. However, the expression and function of Eag1 in liposarcoma are poorly understood. In the present study, the mRNA expression of Eag1 in different adipose tissue samples was examined by real-time PCR. Then, the protein expression of Eag1 in 131 different adipose tissues from 109 patients was detected by immunohistochemistry. Next, the associations between Eag1 expression and clinicopathological features of liposarcoma were analyzed. In addition, the effects of Eag1 on liposarcoma cell proliferation and cycle were evaluated by CCK-8, colony formation, xenograft mouse model, and flow cytometry, respectively. Finally, the activation of p38 mitogen-activated protein kinase (MAPK) was detected by Western blot analysis to explain the detailed mechanisms of oncogenic potential of Eag1 in liposarcoma. It was found that Eag1 was aberrantly expressed in over 67% liposarcomas, with a higher frequency than in lipoma, hyperplasia, inflammation, and normal adipose tissues. However, Eag1 expression was not correlated with clinicopathological features of liposarcoma. Eag1 inhibitor imipramine or Eag1-shRNA significantly suppressed the proliferation of liposarcoma cells in vitro and in vivo, accompanying with accumulation of cells in the G1 phase. These results suggest that Eag1 plays an important role in regulating the proliferation and cell cycle of liposarcoma cells and might be a potential therapeutic target for liposarcoma.

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The effects of Eag1 silencing on the progression of cell cycle. Cells were infected with shRNA for 48 h. (a) Eag1 silence induced a significant increase in SW-872 cells arrested in the G1 phase (P < 0.01, n = 3) and a decrease in cells arrested in the G2 phase, while it demonstrated no effect on the S phases of the cell cycle. Representative images of negative control, Ad5-Control-shRNA, and Ad5-Eag1-shRNA group. (b) Similar results were obtained from 93T449 cells.
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fig5: The effects of Eag1 silencing on the progression of cell cycle. Cells were infected with shRNA for 48 h. (a) Eag1 silence induced a significant increase in SW-872 cells arrested in the G1 phase (P < 0.01, n = 3) and a decrease in cells arrested in the G2 phase, while it demonstrated no effect on the S phases of the cell cycle. Representative images of negative control, Ad5-Control-shRNA, and Ad5-Eag1-shRNA group. (b) Similar results were obtained from 93T449 cells.

Mentions: To determine how Eag1 knockdown inhibits liposarcoma growth, we analyzed DNA contents of SW-872 and 93T449 cells by flow cytometry. As shown in Figure 5, Ad5-Eag1-shRNA led to accumulation of cells in the G1 phase (n = 3, P < 0.01) and reduction of cells in the G2 phase, while it demonstrated no effect on the S phases of the cell cycle in two liposarcoma cell lines. The results suggested that Eag1 is important for the cell cycle of SW-872 and 93T449 cells which are consistent with conclusions reported by others that Eag1 is necessary for progression through the G1 phase and G0/G1 transition of the cell cycle [21].


Potassium channel ether à go-go1 is aberrantly expressed in human liposarcoma and promotes tumorigenesis.

Wu J, Zhong D, Wei Y, Wu X, Kang L, Ding Z - Biomed Res Int (2014)

The effects of Eag1 silencing on the progression of cell cycle. Cells were infected with shRNA for 48 h. (a) Eag1 silence induced a significant increase in SW-872 cells arrested in the G1 phase (P < 0.01, n = 3) and a decrease in cells arrested in the G2 phase, while it demonstrated no effect on the S phases of the cell cycle. Representative images of negative control, Ad5-Control-shRNA, and Ad5-Eag1-shRNA group. (b) Similar results were obtained from 93T449 cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127296&req=5

fig5: The effects of Eag1 silencing on the progression of cell cycle. Cells were infected with shRNA for 48 h. (a) Eag1 silence induced a significant increase in SW-872 cells arrested in the G1 phase (P < 0.01, n = 3) and a decrease in cells arrested in the G2 phase, while it demonstrated no effect on the S phases of the cell cycle. Representative images of negative control, Ad5-Control-shRNA, and Ad5-Eag1-shRNA group. (b) Similar results were obtained from 93T449 cells.
Mentions: To determine how Eag1 knockdown inhibits liposarcoma growth, we analyzed DNA contents of SW-872 and 93T449 cells by flow cytometry. As shown in Figure 5, Ad5-Eag1-shRNA led to accumulation of cells in the G1 phase (n = 3, P < 0.01) and reduction of cells in the G2 phase, while it demonstrated no effect on the S phases of the cell cycle in two liposarcoma cell lines. The results suggested that Eag1 is important for the cell cycle of SW-872 and 93T449 cells which are consistent with conclusions reported by others that Eag1 is necessary for progression through the G1 phase and G0/G1 transition of the cell cycle [21].

Bottom Line: The ether à go-go1 (Eag1) channel is overexpressed in a variety of cancers.Then, the protein expression of Eag1 in 131 different adipose tissues from 109 patients was detected by immunohistochemistry.It was found that Eag1 was aberrantly expressed in over 67% liposarcomas, with a higher frequency than in lipoma, hyperplasia, inflammation, and normal adipose tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhanghua Road 269, Zhangzhou 363000, China.

ABSTRACT
The ether à go-go1 (Eag1) channel is overexpressed in a variety of cancers. However, the expression and function of Eag1 in liposarcoma are poorly understood. In the present study, the mRNA expression of Eag1 in different adipose tissue samples was examined by real-time PCR. Then, the protein expression of Eag1 in 131 different adipose tissues from 109 patients was detected by immunohistochemistry. Next, the associations between Eag1 expression and clinicopathological features of liposarcoma were analyzed. In addition, the effects of Eag1 on liposarcoma cell proliferation and cycle were evaluated by CCK-8, colony formation, xenograft mouse model, and flow cytometry, respectively. Finally, the activation of p38 mitogen-activated protein kinase (MAPK) was detected by Western blot analysis to explain the detailed mechanisms of oncogenic potential of Eag1 in liposarcoma. It was found that Eag1 was aberrantly expressed in over 67% liposarcomas, with a higher frequency than in lipoma, hyperplasia, inflammation, and normal adipose tissues. However, Eag1 expression was not correlated with clinicopathological features of liposarcoma. Eag1 inhibitor imipramine or Eag1-shRNA significantly suppressed the proliferation of liposarcoma cells in vitro and in vivo, accompanying with accumulation of cells in the G1 phase. These results suggest that Eag1 plays an important role in regulating the proliferation and cell cycle of liposarcoma cells and might be a potential therapeutic target for liposarcoma.

Show MeSH
Related in: MedlinePlus