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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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Related in: MedlinePlus

Immunohistochemical staining of Eag1 in different liposarcoma samples. Examples of high expression levels of Eag1 in myxoid liposarcoma (a), pleomorphic liposarcoma (b), round cell liposarcoma (c), and well differentiated liposarcoma (d). Low expression levels of Eag1 are shown in myxoid liposarcoma (e), pleomorphic liposarcoma (f), round cell liposarcoma (g), and well differentiated liposarcoma (h). Magnification: 40x.
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fig2: Immunohistochemical staining of Eag1 in different liposarcoma samples. Examples of high expression levels of Eag1 in myxoid liposarcoma (a), pleomorphic liposarcoma (b), round cell liposarcoma (c), and well differentiated liposarcoma (d). Low expression levels of Eag1 are shown in myxoid liposarcoma (e), pleomorphic liposarcoma (f), round cell liposarcoma (g), and well differentiated liposarcoma (h). Magnification: 40x.

Mentions: Histological subtype based on morphologic appearance of the tumor is the most important prognostic factor for survival. Previous studies have shown that well differentiated liposarcoma and myxoid have favorable prognosis while poorly differentiated liposarcomas have a poor prognosis [20]. To investigate the correlation between Eag1 expression level and liposarcoma histology and/or clinical outcome, we analyzed Eag1 expression level using the score system (staining intensities of 1+ were considered as low Eag1 expression and 2-3+ were considered as high Eag1 expression); Eag1 expression in different liposarcoma histological subtypes was shown in Figure 2. High Eag1 expression was detected in 23 cases (42.6% of the positive expression cases), while the other 31 cases (57.4%) showed low Eag1 expression. There was a clear difference in Eag1 expression levels between well differentiated liposarcoma (21.1%) and pleomorphic/round cell liposarcoma. Meanwhile the high expression rate of Eag1 in myxoid liposarcoma (40.0%) was lower than in pleomorphic and round cell liposarcoma (66.7% and 63.6%, resp.), but the difference was not statistically significant (Table 3).


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)

Immunohistochemical staining of Eag1 in different liposarcoma samples. Examples of high expression levels of Eag1 in myxoid liposarcoma (a), pleomorphic liposarcoma (b), round cell liposarcoma (c), and well differentiated liposarcoma (d). Low expression levels of Eag1 are shown in myxoid liposarcoma (e), pleomorphic liposarcoma (f), round cell liposarcoma (g), and well differentiated liposarcoma (h). Magnification: 40x.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Immunohistochemical staining of Eag1 in different liposarcoma samples. Examples of high expression levels of Eag1 in myxoid liposarcoma (a), pleomorphic liposarcoma (b), round cell liposarcoma (c), and well differentiated liposarcoma (d). Low expression levels of Eag1 are shown in myxoid liposarcoma (e), pleomorphic liposarcoma (f), round cell liposarcoma (g), and well differentiated liposarcoma (h). Magnification: 40x.
Mentions: Histological subtype based on morphologic appearance of the tumor is the most important prognostic factor for survival. Previous studies have shown that well differentiated liposarcoma and myxoid have favorable prognosis while poorly differentiated liposarcomas have a poor prognosis [20]. To investigate the correlation between Eag1 expression level and liposarcoma histology and/or clinical outcome, we analyzed Eag1 expression level using the score system (staining intensities of 1+ were considered as low Eag1 expression and 2-3+ were considered as high Eag1 expression); Eag1 expression in different liposarcoma histological subtypes was shown in Figure 2. High Eag1 expression was detected in 23 cases (42.6% of the positive expression cases), while the other 31 cases (57.4%) showed low Eag1 expression. There was a clear difference in Eag1 expression levels between well differentiated liposarcoma (21.1%) and pleomorphic/round cell liposarcoma. Meanwhile the high expression rate of Eag1 in myxoid liposarcoma (40.0%) was lower than in pleomorphic and round cell liposarcoma (66.7% and 63.6%, resp.), but the difference was not statistically significant (Table 3).

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