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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

Expression level of human TERE1 and hTERT in bladder carcinoma tissues(A) Immunohistochemical staining of normal bladder and bladder carcinoma tissues. (A1–A2) Haematoxylin and eosin staining; (A3–A4): TERE1 staining; (A5–A6): hTERT staining. IHC: immunohistochemistry. Scale bar, 50 μm. (B) mRNA expression level of human TERE1 and hTERT in normal bladder tissue (N) and bladder carcinoma tissue (C). Relative intensities of bands are graphed. Values are means±S.D. of three separate experiments. (C) Analysis of TERE1 and hTERT level in normal and carcinoma bladder tissues with Western blot.
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Figure 1: Expression level of human TERE1 and hTERT in bladder carcinoma tissues(A) Immunohistochemical staining of normal bladder and bladder carcinoma tissues. (A1–A2) Haematoxylin and eosin staining; (A3–A4): TERE1 staining; (A5–A6): hTERT staining. IHC: immunohistochemistry. Scale bar, 50 μm. (B) mRNA expression level of human TERE1 and hTERT in normal bladder tissue (N) and bladder carcinoma tissue (C). Relative intensities of bands are graphed. Values are means±S.D. of three separate experiments. (C) Analysis of TERE1 and hTERT level in normal and carcinoma bladder tissues with Western blot.

Mentions: A total of 83 pathologically proven TCC samples were obtained at surgery from Chinese patients (Table 1). Immunohistochemical staining with TERE1 and hTERT antibodies revealed that, in normal bladder tissues, TERE1 is abundant, and hTERT is barely detectable. In bladder carcinoma tissues, TERE1 is down-regulated and hTERT is up-regulated (Figure 1A).


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)

Expression level of human TERE1 and hTERT in bladder carcinoma tissues(A) Immunohistochemical staining of normal bladder and bladder carcinoma tissues. (A1–A2) Haematoxylin and eosin staining; (A3–A4): TERE1 staining; (A5–A6): hTERT staining. IHC: immunohistochemistry. Scale bar, 50 μm. (B) mRNA expression level of human TERE1 and hTERT in normal bladder tissue (N) and bladder carcinoma tissue (C). Relative intensities of bands are graphed. Values are means±S.D. of three separate experiments. (C) Analysis of TERE1 and hTERT level in normal and carcinoma bladder tissues with Western blot.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Expression level of human TERE1 and hTERT in bladder carcinoma tissues(A) Immunohistochemical staining of normal bladder and bladder carcinoma tissues. (A1–A2) Haematoxylin and eosin staining; (A3–A4): TERE1 staining; (A5–A6): hTERT staining. IHC: immunohistochemistry. Scale bar, 50 μm. (B) mRNA expression level of human TERE1 and hTERT in normal bladder tissue (N) and bladder carcinoma tissue (C). Relative intensities of bands are graphed. Values are means±S.D. of three separate experiments. (C) Analysis of TERE1 and hTERT level in normal and carcinoma bladder tissues with Western blot.
Mentions: A total of 83 pathologically proven TCC samples were obtained at surgery from Chinese patients (Table 1). Immunohistochemical staining with TERE1 and hTERT antibodies revealed that, in normal bladder tissues, TERE1 is abundant, and hTERT is barely detectable. In bladder carcinoma tissues, TERE1 is down-regulated and hTERT is up-regulated (Figure 1A).

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