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Role of estrogen in lung cancer based on the estrogen receptor-epithelial mesenchymal transduction signaling pathways.

Zhao XZ, Liu Y, Zhou LJ, Wang ZQ, Wu ZH, Yang XY - Onco Targets Ther (2015)

Bottom Line: In the present study, we investigated the underlying mechanism of estrogen effect in lung cancer through estrogen receptor-epithelial-mesechymal-transition signaling pathways for the first time.In the estrogen plus tamoxifen group, tamoxifen treatment dramatically reduced protein expression of ERα, ERβ, AKT, and vimentin but significantly increased protein expression of E-cadherin in tumor tissues and lung tissue compared with the estrogen group. mRNA expression of ERβ, PI3K, and AKT was dramatically reduced by tamoxifen treatment in lung tissues compared with the estrogen group.Estrogen promoted lung adenocarcinoma cell metastasis by inducing lung epithelial mesenchymal cells and reducing intercellular adhesion force through PI3K/AKT signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

ABSTRACT

Background/aim: Estrogen is reported to promote the occurrence and development of several human cancers. Increasing evidence shows that most human lung tumors exert estrogen receptor expression. In the present study, we investigated the underlying mechanism of estrogen effect in lung cancer through estrogen receptor-epithelial-mesechymal-transition signaling pathways for the first time.

Materials and methods: A total of 36 inbred C57BL/6 mice (18 male and 18 female) were injected subcutaneously with human lung adenocarcinoma cell line, Lewis. After the lung tumor model was established, mice with lung adenocarcinoma were randomly divided into three groups for each sex (n=6), such as vehicle group, estrogen group, and estrogen plus tamoxifen group. The six groups of mice were sacrificed after 21 days of drug treatment. Tumor tissue was stripped and weighed, and tumor inhibition rate was calculated based on average tumor weight. Protein and messenger RNA (mRNA) expressions of estrogen receptor α (ERα), estrogen receptor β (ERβ), phosphatidylinositol 3'-kinase (PI3K), AKT, E-cadherin, and vimentin were detected in both tumor tissue and lung tissue by using immunohistochemistry and real-time reverse transcription-polymerase chain reaction.

Results: 1) For male mice: in the estrogen group, estrogen treatment significantly increased ERα protein and mRNA expressions in tumor tissue and protein expression of PI3K, AKT, and vimentin in both tumor tissue and lung tissue compared with the vehicle-treated group. Besides, mRNA expression of E-cadherin was significantly reduced in estrogen-treated tumor tissues than that in vehicle-treated tissues. In the estrogen plus tamoxifen group, protein and mRNA expressions of ERα and AKT were dramatically reduced by tamoxifen treatment in tumor tissue compared with the estrogen group; mRNA expression of E-cadherin was increased in tumor tissue; protein expression of vimentin and PI3K were downregulated in tumor tissue; protein expression of E-cadherin increased in lung tissue; protein expression of ERα and PI3K were downregulated in lung tissue compared with the estrogen group. 2) For female mice: in the estrogen group, estrogen treatment significantly increased mRNA expression of ERβ and PI3K, and protein expression of ERβ, PI3K, AKT, and vimentin in both tumor tissue and lung tissue compared with the vehicle-treated group. mRNA expression of E-cadherin was downregulated in tumor tissue, and mRNA expression of AKT was increased in lung tissues compared with the vehicle-treated group. In the estrogen plus tamoxifen group, tamoxifen treatment dramatically reduced protein expression of ERα, ERβ, AKT, and vimentin but significantly increased protein expression of E-cadherin in tumor tissues and lung tissue compared with the estrogen group. mRNA expression of ERβ, PI3K, and AKT was dramatically reduced by tamoxifen treatment in lung tissues compared with the estrogen group.

Conclusion: Estrogen promoted lung adenocarcinoma cell metastasis by inducing lung epithelial mesenchymal cells and reducing intercellular adhesion force through PI3K/AKT signaling pathway.

No MeSH data available.


Related in: MedlinePlus

Tumor tissue weight and tumor inhibition rate.Notes: (A) The average tumor tissue weight in different groups. (B) The tumor inhibition rate in various groups. *P<0.05 versus the estrogen group and #P<0.05 versus the vehicle group.
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f2-ott-8-2849: Tumor tissue weight and tumor inhibition rate.Notes: (A) The average tumor tissue weight in different groups. (B) The tumor inhibition rate in various groups. *P<0.05 versus the estrogen group and #P<0.05 versus the vehicle group.

Mentions: In female mice, the average tumor weight in the estrogen group was significantly upregulated than that in the vehicle group. Compared with the estrogen group, the average tumor weight in the estrogen plus tamoxifen group was dramatically decreased (Figure 2A). The tumor inhibition rate = (1− the average tumor weight of therapy group/the average tumor weight of model group) ×100%. The tumor inhibition rate for two estrogen groups was all negative (Figure 2B).


Role of estrogen in lung cancer based on the estrogen receptor-epithelial mesenchymal transduction signaling pathways.

Zhao XZ, Liu Y, Zhou LJ, Wang ZQ, Wu ZH, Yang XY - Onco Targets Ther (2015)

Tumor tissue weight and tumor inhibition rate.Notes: (A) The average tumor tissue weight in different groups. (B) The tumor inhibition rate in various groups. *P<0.05 versus the estrogen group and #P<0.05 versus the vehicle group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608546&req=5

f2-ott-8-2849: Tumor tissue weight and tumor inhibition rate.Notes: (A) The average tumor tissue weight in different groups. (B) The tumor inhibition rate in various groups. *P<0.05 versus the estrogen group and #P<0.05 versus the vehicle group.
Mentions: In female mice, the average tumor weight in the estrogen group was significantly upregulated than that in the vehicle group. Compared with the estrogen group, the average tumor weight in the estrogen plus tamoxifen group was dramatically decreased (Figure 2A). The tumor inhibition rate = (1− the average tumor weight of therapy group/the average tumor weight of model group) ×100%. The tumor inhibition rate for two estrogen groups was all negative (Figure 2B).

Bottom Line: In the present study, we investigated the underlying mechanism of estrogen effect in lung cancer through estrogen receptor-epithelial-mesechymal-transition signaling pathways for the first time.In the estrogen plus tamoxifen group, tamoxifen treatment dramatically reduced protein expression of ERα, ERβ, AKT, and vimentin but significantly increased protein expression of E-cadherin in tumor tissues and lung tissue compared with the estrogen group. mRNA expression of ERβ, PI3K, and AKT was dramatically reduced by tamoxifen treatment in lung tissues compared with the estrogen group.Estrogen promoted lung adenocarcinoma cell metastasis by inducing lung epithelial mesenchymal cells and reducing intercellular adhesion force through PI3K/AKT signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

ABSTRACT

Background/aim: Estrogen is reported to promote the occurrence and development of several human cancers. Increasing evidence shows that most human lung tumors exert estrogen receptor expression. In the present study, we investigated the underlying mechanism of estrogen effect in lung cancer through estrogen receptor-epithelial-mesechymal-transition signaling pathways for the first time.

Materials and methods: A total of 36 inbred C57BL/6 mice (18 male and 18 female) were injected subcutaneously with human lung adenocarcinoma cell line, Lewis. After the lung tumor model was established, mice with lung adenocarcinoma were randomly divided into three groups for each sex (n=6), such as vehicle group, estrogen group, and estrogen plus tamoxifen group. The six groups of mice were sacrificed after 21 days of drug treatment. Tumor tissue was stripped and weighed, and tumor inhibition rate was calculated based on average tumor weight. Protein and messenger RNA (mRNA) expressions of estrogen receptor α (ERα), estrogen receptor β (ERβ), phosphatidylinositol 3'-kinase (PI3K), AKT, E-cadherin, and vimentin were detected in both tumor tissue and lung tissue by using immunohistochemistry and real-time reverse transcription-polymerase chain reaction.

Results: 1) For male mice: in the estrogen group, estrogen treatment significantly increased ERα protein and mRNA expressions in tumor tissue and protein expression of PI3K, AKT, and vimentin in both tumor tissue and lung tissue compared with the vehicle-treated group. Besides, mRNA expression of E-cadherin was significantly reduced in estrogen-treated tumor tissues than that in vehicle-treated tissues. In the estrogen plus tamoxifen group, protein and mRNA expressions of ERα and AKT were dramatically reduced by tamoxifen treatment in tumor tissue compared with the estrogen group; mRNA expression of E-cadherin was increased in tumor tissue; protein expression of vimentin and PI3K were downregulated in tumor tissue; protein expression of E-cadherin increased in lung tissue; protein expression of ERα and PI3K were downregulated in lung tissue compared with the estrogen group. 2) For female mice: in the estrogen group, estrogen treatment significantly increased mRNA expression of ERβ and PI3K, and protein expression of ERβ, PI3K, AKT, and vimentin in both tumor tissue and lung tissue compared with the vehicle-treated group. mRNA expression of E-cadherin was downregulated in tumor tissue, and mRNA expression of AKT was increased in lung tissues compared with the vehicle-treated group. In the estrogen plus tamoxifen group, tamoxifen treatment dramatically reduced protein expression of ERα, ERβ, AKT, and vimentin but significantly increased protein expression of E-cadherin in tumor tissues and lung tissue compared with the estrogen group. mRNA expression of ERβ, PI3K, and AKT was dramatically reduced by tamoxifen treatment in lung tissues compared with the estrogen group.

Conclusion: Estrogen promoted lung adenocarcinoma cell metastasis by inducing lung epithelial mesenchymal cells and reducing intercellular adhesion force through PI3K/AKT signaling pathway.

No MeSH data available.


Related in: MedlinePlus