title: Crosstalk between p38 and Smad3 through TGF-β1 in JEG-3 choriocarcinoma cells.
abstract: Choriocarcinoma is a highly malignant trophoblastic tumor related to pregnancy that often occurs with a complete hydatidiform mole. It grows quickly and can also widely metastasize to other organs or tissues through both the venous and lymphatic systems. The transforming growth factor-β1 (TGF-β1) belongs to a growth factor superfamily and has been suggested to play a critical role in regulating the genesis and development of choriocarcinoma through a variety of Smad-independent pathways, including the p38 MAPK pathway. Previous studies indicated that TGF-β can activate the p38 MAPK pathway. In this study, we investigated Smad and p38 MAPK signaling in JEG-3 choriocarcinoma cells using p38 MAPK inhibitor and TGF-β receptor inhibitor. Immunofluorescence and western blot assays were used to detect the proteins in Smad and p38 MAPK pathways. Our data demonstrated that TGF-β can activate Smad3 and induce Smad3 translocation into the nucleus in JEG-3 cells. Blockade of the TGF-β pathway significantly reduced the expression levels of p38 and phospho-p38. p38 MAPK inhibitors (SB 203580) can attenuate TGF-β1-induced Smad3 expression and suppress the activation of smad3. These findings indicate crosstalk between p38 and smad3 through TGF-β1 in choriocarcinoma cells.
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.forename: Yusi
authors.initials: Y
authors.lastname: Tan
authors.forename: Kongyan
authors.initials: K
authors.lastname: Zhang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D011725:Pyridines; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580