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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

Activation of Ras–MAPK signalling in bladder carcinoma tissuesCompared with normal bladder tissues, phosphorylation levels of B-Raf (Ser455), C-Raf (Ser338), MEK (1/2) and ERK significantly increased in bladder carcinoma tissues. The relative intensities of bands are shown in diagram. Values are means±SD of three separate experiments.
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Figure 4: Activation of Ras–MAPK signalling in bladder carcinoma tissuesCompared with normal bladder tissues, phosphorylation levels of B-Raf (Ser455), C-Raf (Ser338), MEK (1/2) and ERK significantly increased in bladder carcinoma tissues. The relative intensities of bands are shown in diagram. Values are means±SD of three separate experiments.

Mentions: To verify the above results in bladder carcinoma tissues, phosphorylation levels of key molecules within the Ras–MAPK signalling pathway such as Raf, MEK and ERK were further measured using Western blot analysis (Figure 4). Compared with normal tissue, phosphorylated protein levels of B-Raf (Ser455), C-Raf (Ser338), MEK (1/2) and ERK increased significantly in bladder carcinoma (P<0.05). However, total protein levels of A-Raf, B-Raf (Ser455), C-Raf (Ser338), MEK (1/2) and ERK as well as the phosphorylation levels of A-Raf (Ser299) in bladder carcinoma tissues bear no significant differences compared with normal bladder tissues. Therefore, down-regulation of TERE1 directly activates Ras–MAPK signalling pathway in bladder carcinoma tissues. The finding is consistent with the results from cell culture experiments. Based upon our results, it is possible that TERE1/UBIAD1 affects the formation of bladder carcinoma through Ras–MAPK signal transduction pathway.


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)

Activation of Ras–MAPK signalling in bladder carcinoma tissuesCompared with normal bladder tissues, phosphorylation levels of B-Raf (Ser455), C-Raf (Ser338), MEK (1/2) and ERK significantly increased in bladder carcinoma tissues. The relative intensities of bands are shown in diagram. Values are means±SD of three separate experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Activation of Ras–MAPK signalling in bladder carcinoma tissuesCompared with normal bladder tissues, phosphorylation levels of B-Raf (Ser455), C-Raf (Ser338), MEK (1/2) and ERK significantly increased in bladder carcinoma tissues. The relative intensities of bands are shown in diagram. Values are means±SD of three separate experiments.
Mentions: To verify the above results in bladder carcinoma tissues, phosphorylation levels of key molecules within the Ras–MAPK signalling pathway such as Raf, MEK and ERK were further measured using Western blot analysis (Figure 4). Compared with normal tissue, phosphorylated protein levels of B-Raf (Ser455), C-Raf (Ser338), MEK (1/2) and ERK increased significantly in bladder carcinoma (P<0.05). However, total protein levels of A-Raf, B-Raf (Ser455), C-Raf (Ser338), MEK (1/2) and ERK as well as the phosphorylation levels of A-Raf (Ser299) in bladder carcinoma tissues bear no significant differences compared with normal bladder tissues. Therefore, down-regulation of TERE1 directly activates Ras–MAPK signalling pathway in bladder carcinoma tissues. The finding is consistent with the results from cell culture experiments. Based upon our results, it is possible that TERE1/UBIAD1 affects the formation of bladder carcinoma through Ras–MAPK signal transduction pathway.

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