title: Crosstalk between the p38 and TGF-β signaling pathways through TβRI, TβRII and Smad3 expression in plancental choriocarcinoma JEG-3 cells.
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.
authors.affiliation: Department of Basic Medicine, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Basic Medicine, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Basic Medicine, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Basic Medicine, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Basic Medicine, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Kongyan
authors.initials: K
authors.lastname: Zhang
keywords: Smad3; TGF-β; TβRI; TβRII; choriocarcinoma; p38 MAPK