Crosstalk between the p38 and TGF‑β signaling pathways through TβRI, TβRII and Smad3 expression in plancental choriocarcinoma JEG‑3 cells

Tan,Yusi; Xu,Qian; Li,Yuhong; Mao,Xiaodan; Zhang,Kongyan

doi:10.3892/ol.2014.2255

Crosstalk between the p38 and TGF‑β signaling pathways through TβRI, TβRII and Smad3 expression in plancental choriocarcinoma JEG‑3 cells

Authors:
- Yusi Tan
- Qian Xu
- Yuhong Li
- Xiaodan Mao
- Kongyan Zhang
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Affiliations: Department of Basic Medicine, Chengde Medical College, Chengde, Hebei 067000, P.R. China
Published online on: June 16, 2014 https://doi.org/10.3892/ol.2014.2255
Pages: 1307-1311

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Abstract

Choriocarcinoma is a highly aggressive tumor that develops from germ cells. Some choriocarcinomas originate in the testes or ovaries, while others may develop in the uterus after a normal pregnancy or after miscarriage. The tumor is characterized by early hematogenous spread to distal organs, such as the lung and brain. Transforming growth factor β1 (TGF‑β1) is key in regulating tumor cell proliferation and invasion through a variety of Smad‑dependent and ‑independent pathways, including the p38 mitogen‑activated protein kinase (MAPK) pathway. There appears to be crosstalk between the TGF‑β/Smad and p38 MAPK pathways; however, the molecular mechanisms underlying the crosstalk are not fully understood. The present study validated the role of TGF‑β signaling in cancer progression and explored the interaction between Smad and p38 MAPK signaling on transduction mediators in choriocarcinoma using the JEG‑3 cell line. MTT assay was used to detect the effect of TGF‑β1 on JEG‑3 cell proliferation. Cells were treated with p38 MAPK inhibitor and TGF‑β receptor inhibitor, followed by TGF‑β1, and reverse transcription quantitative real‑time polymerase chain reaction was used to examine the transcriptional levels of Smad3 and TGF‑β receptors. The data demonstrated that TGF‑β can enhance the viability of JEG‑3 cells. Blockade of the TGF‑β and p38 MAPK pathways attenuated the expression of Smad3, TGF‑β receptor type I (TβRI) and TβRII, and inhibited their expression in a dose‑dependent manner. Analysis revealed that p38 MAPK is involved in and contributes to the TGF‑β pathway, dependent on the regulation of TβRI, TβRII and Smad3. Further investigation of the interactions between the TGF‑β and p38 MAPK pathways may offer potential venues for therapeutic intervention for choriocarcinoma.

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