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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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Ad5-Eag1-shRNA inhibits liposarcoma growth in vivo. (a) Cartoon representation of the experiment with liposarcoma xenograft tumors and Ad5-Eag1-shRNA treatment. Xenograft tumors are established by subcutaneous injection of 1 × 105 liposarcoma cells. After two weeks, the tumors grow to visible size. Ad5-Eag1-shRNA treatment is given by intratumor injection every third day (blue arrows). Mice in the control group are injected with saline or Ad5-Control-shRNA. (b) The length and width of tumors are measured every third day after inoculation and the volume of tumor is calculated. After 15 days, the tumor volume growth curve is drafted. ∗∗P < 0.01 versus saline or Ad5-Control-shRNA group.
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fig4: Ad5-Eag1-shRNA inhibits liposarcoma growth in vivo. (a) Cartoon representation of the experiment with liposarcoma xenograft tumors and Ad5-Eag1-shRNA treatment. Xenograft tumors are established by subcutaneous injection of 1 × 105 liposarcoma cells. After two weeks, the tumors grow to visible size. Ad5-Eag1-shRNA treatment is given by intratumor injection every third day (blue arrows). Mice in the control group are injected with saline or Ad5-Control-shRNA. (b) The length and width of tumors are measured every third day after inoculation and the volume of tumor is calculated. After 15 days, the tumor volume growth curve is drafted. ∗∗P < 0.01 versus saline or Ad5-Control-shRNA group.

Mentions: To investigate the in vivo role of Eag1 in liposarcoma, we made a xenograft model of liposarcoma using nude mice and treated the xenografts by intratumor injection of Ad5-Eag1-shRNA, Ad5-Control-shRNA, or saline (Figure 4(a)). The results showed that the tumor volume was significantly smaller in Ad5-Eag1-shRNA injected animals than in saline or Ad5-Control-shRNA injected animals at each evaluating time point (Figure 4(b)). These in vivo data confirm our in vitro results and suggest the oncogenic role of Eag1 in liposarcoma.


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)

Ad5-Eag1-shRNA inhibits liposarcoma growth in vivo. (a) Cartoon representation of the experiment with liposarcoma xenograft tumors and Ad5-Eag1-shRNA treatment. Xenograft tumors are established by subcutaneous injection of 1 × 105 liposarcoma cells. After two weeks, the tumors grow to visible size. Ad5-Eag1-shRNA treatment is given by intratumor injection every third day (blue arrows). Mice in the control group are injected with saline or Ad5-Control-shRNA. (b) The length and width of tumors are measured every third day after inoculation and the volume of tumor is calculated. After 15 days, the tumor volume growth curve is drafted. ∗∗P < 0.01 versus saline or Ad5-Control-shRNA group.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Ad5-Eag1-shRNA inhibits liposarcoma growth in vivo. (a) Cartoon representation of the experiment with liposarcoma xenograft tumors and Ad5-Eag1-shRNA treatment. Xenograft tumors are established by subcutaneous injection of 1 × 105 liposarcoma cells. After two weeks, the tumors grow to visible size. Ad5-Eag1-shRNA treatment is given by intratumor injection every third day (blue arrows). Mice in the control group are injected with saline or Ad5-Control-shRNA. (b) The length and width of tumors are measured every third day after inoculation and the volume of tumor is calculated. After 15 days, the tumor volume growth curve is drafted. ∗∗P < 0.01 versus saline or Ad5-Control-shRNA group.
Mentions: To investigate the in vivo role of Eag1 in liposarcoma, we made a xenograft model of liposarcoma using nude mice and treated the xenografts by intratumor injection of Ad5-Eag1-shRNA, Ad5-Control-shRNA, or saline (Figure 4(a)). The results showed that the tumor volume was significantly smaller in Ad5-Eag1-shRNA injected animals than in saline or Ad5-Control-shRNA injected animals at each evaluating time point (Figure 4(b)). These in vivo data confirm our in vitro results and suggest the oncogenic role of Eag1 in liposarcoma.

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