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

Tan Y, Xu Q, Li Y, Mao X, Zhang K - Oncol Lett (2014)

Bottom Line: MTT assay was used to detect the effect of TGF-β1 on JEG-3 cell proliferation.The data demonstrated that TGF-β can enhance the viability of JEG-3 cells.Analysis revealed that p38 MAPK is involved in and contributes to the TGF-β pathway, dependent on the regulation of TβRI, TβRII and Smad3.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Medicine, Chengde Medical College, Chengde, Hebei 067000, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of p38 MAPK inhibition on TβRI transcriptional levels in the JEG-3 cell line. Cells were divided into six groups: Control group, TGF-β1 group, 1-μM SB203580, 3-μM SB203580, 1-μM LY364947 and 3-μM LY364947 groups. Cells were pretreated with different concentrations of p38 MAPK and TGF-β1 receptor inhibitors, and cultured for 2 h. Next, 5 ng/ml TGF-β1 was added to cells in all groups except the control group, and incubation was continued for 2 h. The mRNA expression levels of TβRI were determined by reverse transcription quantitative real-time polymerase chain reaction. Results are presented as the mean ± SD from at least three independent experiments (P<0.05). MAPK, mitogen-activated protein kinase; TGF-β1, transforming growth factor β1; TβRI, TGF-β receptor type I. *P<0.05 vs. control group; ΔP<0.01 vs. TGF-β1 group.
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f3-ol-08-03-1307: Effect of p38 MAPK inhibition on TβRI transcriptional levels in the JEG-3 cell line. Cells were divided into six groups: Control group, TGF-β1 group, 1-μM SB203580, 3-μM SB203580, 1-μM LY364947 and 3-μM LY364947 groups. Cells were pretreated with different concentrations of p38 MAPK and TGF-β1 receptor inhibitors, and cultured for 2 h. Next, 5 ng/ml TGF-β1 was added to cells in all groups except the control group, and incubation was continued for 2 h. The mRNA expression levels of TβRI were determined by reverse transcription quantitative real-time polymerase chain reaction. Results are presented as the mean ± SD from at least three independent experiments (P<0.05). MAPK, mitogen-activated protein kinase; TGF-β1, transforming growth factor β1; TβRI, TGF-β receptor type I. *P<0.05 vs. control group; ΔP<0.01 vs. TGF-β1 group.

Mentions: In order to examine the roles of TβRI and TβRII in the regulation of p38 MAPK, the TβRI and TβRII transcriptional levels were examined by blocking p38 MAPK using a p38 MAPK inhibitor, SB203580. The mRNA expression levels of TβRI and TβRII in the TGF-β1 group were both increased compared with those in the control group (P<0.05). Pretreatment with LY36494, a TGF-β-1 inhibitor, resulted in significant decrease (P<0.05) in the mRNA levels of TβRI, in a dose-dependent manner, compared with those of the TGF-β1 group. In the groups treated with SB203580, the trend of TβRI transcriptional levels was similar to that in the LY36494-treated groups, which indicated that the p38 MAPK inhibitor downregulates the TβRI transcriptional level (P<0.05) (Fig. 3).


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

Tan Y, Xu Q, Li Y, Mao X, Zhang K - Oncol Lett (2014)

Effect of p38 MAPK inhibition on TβRI transcriptional levels in the JEG-3 cell line. Cells were divided into six groups: Control group, TGF-β1 group, 1-μM SB203580, 3-μM SB203580, 1-μM LY364947 and 3-μM LY364947 groups. Cells were pretreated with different concentrations of p38 MAPK and TGF-β1 receptor inhibitors, and cultured for 2 h. Next, 5 ng/ml TGF-β1 was added to cells in all groups except the control group, and incubation was continued for 2 h. The mRNA expression levels of TβRI were determined by reverse transcription quantitative real-time polymerase chain reaction. Results are presented as the mean ± SD from at least three independent experiments (P<0.05). MAPK, mitogen-activated protein kinase; TGF-β1, transforming growth factor β1; TβRI, TGF-β receptor type I. *P<0.05 vs. control group; ΔP<0.01 vs. TGF-β1 group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4114612&req=5

f3-ol-08-03-1307: Effect of p38 MAPK inhibition on TβRI transcriptional levels in the JEG-3 cell line. Cells were divided into six groups: Control group, TGF-β1 group, 1-μM SB203580, 3-μM SB203580, 1-μM LY364947 and 3-μM LY364947 groups. Cells were pretreated with different concentrations of p38 MAPK and TGF-β1 receptor inhibitors, and cultured for 2 h. Next, 5 ng/ml TGF-β1 was added to cells in all groups except the control group, and incubation was continued for 2 h. The mRNA expression levels of TβRI were determined by reverse transcription quantitative real-time polymerase chain reaction. Results are presented as the mean ± SD from at least three independent experiments (P<0.05). MAPK, mitogen-activated protein kinase; TGF-β1, transforming growth factor β1; TβRI, TGF-β receptor type I. *P<0.05 vs. control group; ΔP<0.01 vs. TGF-β1 group.
Mentions: In order to examine the roles of TβRI and TβRII in the regulation of p38 MAPK, the TβRI and TβRII transcriptional levels were examined by blocking p38 MAPK using a p38 MAPK inhibitor, SB203580. The mRNA expression levels of TβRI and TβRII in the TGF-β1 group were both increased compared with those in the control group (P<0.05). Pretreatment with LY36494, a TGF-β-1 inhibitor, resulted in significant decrease (P<0.05) in the mRNA levels of TβRI, in a dose-dependent manner, compared with those of the TGF-β1 group. In the groups treated with SB203580, the trend of TβRI transcriptional levels was similar to that in the LY36494-treated groups, which indicated that the p38 MAPK inhibitor downregulates the TβRI transcriptional level (P<0.05) (Fig. 3).

Bottom Line: MTT assay was used to detect the effect of TGF-β1 on JEG-3 cell proliferation.The data demonstrated that TGF-β can enhance the viability of JEG-3 cells.Analysis revealed that p38 MAPK is involved in and contributes to the TGF-β pathway, dependent on the regulation of TβRI, TβRII and Smad3.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Medicine, Chengde Medical College, Chengde, Hebei 067000, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus