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Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell proliferation.

Xia Y, Wei X, Wu S, Wang B, Wang X, Hong L - Cell Biol Int Rep (2010) (2010)

Bottom Line: It was found that decreased TERE1/UBIAD1 expression is closely related to both an increased hTERT expression and activation of Ras-MAPK signalling.When the levels of hTERT expression and ERK phosphorylation were measured, it was found that both of them increased in the above transfected cells, suggesting the activation of Ras-MAPK signalling.Our result is the initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling and induces subsequent cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Peoples Republic of China ; †Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China.

ABSTRACT
TERE1/UBIAD1 is involved in SCCD (Schnyder crystalline corneal dystrophy) and multiple human cancers. So far, the molecular mechanism of TERE1/UBIAD1 in tumourigenesis is unclear. Here, the expression levels of hTERT and TERE1/UBIAD1 in pathologically proven Chinese TCC (transitional cell carcinoma) samples were measured. It was found that decreased TERE1/UBIAD1 expression is closely related to both an increased hTERT expression and activation of Ras-MAPK signalling. Chemically modified TERE1 siRNA oligos were used to knock down TERE1 expression in human L02 cells. Cells transfected with TERE1 siRNA oligos underwent significant cell proliferation. When the levels of hTERT expression and ERK phosphorylation were measured, it was found that both of them increased in the above transfected cells, suggesting the activation of Ras-MAPK signalling. Addition of the MEK inhibitor U0126 into the transfected L02 cells described above inhibited ERK phosphorylation and hTERT expression. Our result is the initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling and induces subsequent cell proliferation. TERE1 might be a new negative regulator of Ras-MAPK signalling, which plays a pivotal role in the cell proliferation of multiple human cancers.

No MeSH data available.


Related in: MedlinePlus

U0126 partially blocking the activation of Ras–MAPK signalling induced by TERE1 down-regulation(A) T24 cells treated with U0126 showed decreased hTERT expression in both mRNA and protein levels. (B) ERK phosphorylation is inhibited by U0126 in T24 cells. (C) Human L02 cells transfected with TERE1 291- and 322-siRNA oligos and pretreated with U0126 (middle panel) showed decreased mRNA level of hTERT compared with samples without U0126 (upper panel). (D) Human L02 cells transfected with TERE1 291- and 322-siRNA oligos were treated with U0126, which decreased hTERT expression and ERK phosphorylation. The intensities of the bands were compared in the diagram.
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Figure 5: U0126 partially blocking the activation of Ras–MAPK signalling induced by TERE1 down-regulation(A) T24 cells treated with U0126 showed decreased hTERT expression in both mRNA and protein levels. (B) ERK phosphorylation is inhibited by U0126 in T24 cells. (C) Human L02 cells transfected with TERE1 291- and 322-siRNA oligos and pretreated with U0126 (middle panel) showed decreased mRNA level of hTERT compared with samples without U0126 (upper panel). (D) Human L02 cells transfected with TERE1 291- and 322-siRNA oligos were treated with U0126, which decreased hTERT expression and ERK phosphorylation. The intensities of the bands were compared in the diagram.

Mentions: Since Ras–MAPK signalling is involved in the activation of hTERT expression and cell proliferation in TERE1 down-regulated cells, tests were performed to determine if inhibition of MAPK phosphorylation would decrease hTERT expression. T24 cell lines pretreated with U0126 (an MEK1/2-specific inhibitor) showed decreased hTERT expression in both mRNA and protein levels (Figure 5A). In addition, the level of ERK phosphorylation in T24 cells pretreated with U0126 decreased as expected (Figure 5B). This result indicates that the inhibition of ERK phosphorylation will partially decrease the expression of hTERT.


Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell proliferation.

Xia Y, Wei X, Wu S, Wang B, Wang X, Hong L - Cell Biol Int Rep (2010) (2010)

U0126 partially blocking the activation of Ras–MAPK signalling induced by TERE1 down-regulation(A) T24 cells treated with U0126 showed decreased hTERT expression in both mRNA and protein levels. (B) ERK phosphorylation is inhibited by U0126 in T24 cells. (C) Human L02 cells transfected with TERE1 291- and 322-siRNA oligos and pretreated with U0126 (middle panel) showed decreased mRNA level of hTERT compared with samples without U0126 (upper panel). (D) Human L02 cells transfected with TERE1 291- and 322-siRNA oligos were treated with U0126, which decreased hTERT expression and ERK phosphorylation. The intensities of the bands were compared in the diagram.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475436&req=5

Figure 5: U0126 partially blocking the activation of Ras–MAPK signalling induced by TERE1 down-regulation(A) T24 cells treated with U0126 showed decreased hTERT expression in both mRNA and protein levels. (B) ERK phosphorylation is inhibited by U0126 in T24 cells. (C) Human L02 cells transfected with TERE1 291- and 322-siRNA oligos and pretreated with U0126 (middle panel) showed decreased mRNA level of hTERT compared with samples without U0126 (upper panel). (D) Human L02 cells transfected with TERE1 291- and 322-siRNA oligos were treated with U0126, which decreased hTERT expression and ERK phosphorylation. The intensities of the bands were compared in the diagram.
Mentions: Since Ras–MAPK signalling is involved in the activation of hTERT expression and cell proliferation in TERE1 down-regulated cells, tests were performed to determine if inhibition of MAPK phosphorylation would decrease hTERT expression. T24 cell lines pretreated with U0126 (an MEK1/2-specific inhibitor) showed decreased hTERT expression in both mRNA and protein levels (Figure 5A). In addition, the level of ERK phosphorylation in T24 cells pretreated with U0126 decreased as expected (Figure 5B). This result indicates that the inhibition of ERK phosphorylation will partially decrease the expression of hTERT.

Bottom Line: It was found that decreased TERE1/UBIAD1 expression is closely related to both an increased hTERT expression and activation of Ras-MAPK signalling.When the levels of hTERT expression and ERK phosphorylation were measured, it was found that both of them increased in the above transfected cells, suggesting the activation of Ras-MAPK signalling.Our result is the initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling and induces subsequent cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Peoples Republic of China ; †Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China.

ABSTRACT
TERE1/UBIAD1 is involved in SCCD (Schnyder crystalline corneal dystrophy) and multiple human cancers. So far, the molecular mechanism of TERE1/UBIAD1 in tumourigenesis is unclear. Here, the expression levels of hTERT and TERE1/UBIAD1 in pathologically proven Chinese TCC (transitional cell carcinoma) samples were measured. It was found that decreased TERE1/UBIAD1 expression is closely related to both an increased hTERT expression and activation of Ras-MAPK signalling. Chemically modified TERE1 siRNA oligos were used to knock down TERE1 expression in human L02 cells. Cells transfected with TERE1 siRNA oligos underwent significant cell proliferation. When the levels of hTERT expression and ERK phosphorylation were measured, it was found that both of them increased in the above transfected cells, suggesting the activation of Ras-MAPK signalling. Addition of the MEK inhibitor U0126 into the transfected L02 cells described above inhibited ERK phosphorylation and hTERT expression. Our result is the initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling and induces subsequent cell proliferation. TERE1 might be a new negative regulator of Ras-MAPK signalling, which plays a pivotal role in the cell proliferation of multiple human cancers.

No MeSH data available.


Related in: MedlinePlus