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Downregulation of human Wnt3 in gastric cancer suppresses cell proliferation and induces apoptosis.

Wang HS, Nie X, Wu RB, Yuan HW, Ma YH, Liu XL, Zhang JY, Deng XL, Na Q, Jin HY, Bian YC, Gao YM, Wang YD, Chen WD - Onco Targets Ther (2016)

Bottom Line: In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues.Silence of Wnt3 expression in gastric cancer cells inhibited the expression of β-catenin and cyclin D1 genes in Wnt/β-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate.Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Pathology, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot.

ABSTRACT
Aberrant activation of Wnt/β-catenin signaling pathways is closely involved in the occurrence and progression of several types of human malignancies. However, as a fundamental component in this cascade, Wnt3 has not been well understood for the expression level and pathogenic mechanism in gastric carcinogenesis. Here, this research was undertaken to elucidate the important role of Wnt3 in gastric cancer. Wnt3 expression in gastric carcinomas and their respective normal tissues was examined by immunoblotting and immunohistochemistry. In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues. Knocking down Wnt3 in MGC-803 gastric cancer cells by small interfering RNAs transfection led to an obvious decrease in both transcript and protein levels. Silence of Wnt3 expression in gastric cancer cells inhibited the expression of β-catenin and cyclin D1 genes in Wnt/β-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate. Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer.

No MeSH data available.


Related in: MedlinePlus

Expression of Wnt3 in human nonneoplastic gastric tissues and gastric cancer tissues.Notes: Representative immunohistochemical staining of Wnt3 in human normal gastric tissues (A) or gastric cancer tissues (B). Magnification ×200. (C and D) Representative immunoblot of Wnt3 protein expression in human gastric cancer and corresponding nontumor tissues by Western blot analysis, normalized to human β-actin protein levels. Data represent the mean ± standard deviation from ten groups of gastric tissues (normal and cancer). *P<0.05 compared with the corresponding adjacent normal gastric tissues.
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f1-ott-9-3849: Expression of Wnt3 in human nonneoplastic gastric tissues and gastric cancer tissues.Notes: Representative immunohistochemical staining of Wnt3 in human normal gastric tissues (A) or gastric cancer tissues (B). Magnification ×200. (C and D) Representative immunoblot of Wnt3 protein expression in human gastric cancer and corresponding nontumor tissues by Western blot analysis, normalized to human β-actin protein levels. Data represent the mean ± standard deviation from ten groups of gastric tissues (normal and cancer). *P<0.05 compared with the corresponding adjacent normal gastric tissues.

Mentions: Emerging evidence has revealed that canonical Wnt pathways play an important role in cellular proliferation and tumorigenesis. In order to determine whether Wnt signaling is aberrantly activated in tumor microenvironment, we examined the Wnt3 protein levels in 20 gastric carcinoma and 20 nonneoplastic gastric samples by immunohistochemical analysis. Wnt3 was found to be overexpressed in gastric cancer samples in contrast to the comparatively lower levels in normal tissues with a statistical significance (P<0.05). Representative sections of Wnt3 expression in tumor tissues and normal ones are shown in Figure 1A and B. In a further effort to validate the earlier findings, we measured the expression of Wnt3 at protein levels in fresh gastric samples. As expected, immunoblot detection demonstrated a similar upregulation of Wnt3 protein level in gastric cancer tissues compared with nontumor ones (Figure 1C and D). Taken together, Wnt3 is upregulated in gastric carcinoma and may exert a carcinogenic effect in the occurrence and development of gastric tumors.


Downregulation of human Wnt3 in gastric cancer suppresses cell proliferation and induces apoptosis.

Wang HS, Nie X, Wu RB, Yuan HW, Ma YH, Liu XL, Zhang JY, Deng XL, Na Q, Jin HY, Bian YC, Gao YM, Wang YD, Chen WD - Onco Targets Ther (2016)

Expression of Wnt3 in human nonneoplastic gastric tissues and gastric cancer tissues.Notes: Representative immunohistochemical staining of Wnt3 in human normal gastric tissues (A) or gastric cancer tissues (B). Magnification ×200. (C and D) Representative immunoblot of Wnt3 protein expression in human gastric cancer and corresponding nontumor tissues by Western blot analysis, normalized to human β-actin protein levels. Data represent the mean ± standard deviation from ten groups of gastric tissues (normal and cancer). *P<0.05 compared with the corresponding adjacent normal gastric tissues.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4930241&req=5

f1-ott-9-3849: Expression of Wnt3 in human nonneoplastic gastric tissues and gastric cancer tissues.Notes: Representative immunohistochemical staining of Wnt3 in human normal gastric tissues (A) or gastric cancer tissues (B). Magnification ×200. (C and D) Representative immunoblot of Wnt3 protein expression in human gastric cancer and corresponding nontumor tissues by Western blot analysis, normalized to human β-actin protein levels. Data represent the mean ± standard deviation from ten groups of gastric tissues (normal and cancer). *P<0.05 compared with the corresponding adjacent normal gastric tissues.
Mentions: Emerging evidence has revealed that canonical Wnt pathways play an important role in cellular proliferation and tumorigenesis. In order to determine whether Wnt signaling is aberrantly activated in tumor microenvironment, we examined the Wnt3 protein levels in 20 gastric carcinoma and 20 nonneoplastic gastric samples by immunohistochemical analysis. Wnt3 was found to be overexpressed in gastric cancer samples in contrast to the comparatively lower levels in normal tissues with a statistical significance (P<0.05). Representative sections of Wnt3 expression in tumor tissues and normal ones are shown in Figure 1A and B. In a further effort to validate the earlier findings, we measured the expression of Wnt3 at protein levels in fresh gastric samples. As expected, immunoblot detection demonstrated a similar upregulation of Wnt3 protein level in gastric cancer tissues compared with nontumor ones (Figure 1C and D). Taken together, Wnt3 is upregulated in gastric carcinoma and may exert a carcinogenic effect in the occurrence and development of gastric tumors.

Bottom Line: In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues.Silence of Wnt3 expression in gastric cancer cells inhibited the expression of β-catenin and cyclin D1 genes in Wnt/β-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate.Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Pathology, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot.

ABSTRACT
Aberrant activation of Wnt/β-catenin signaling pathways is closely involved in the occurrence and progression of several types of human malignancies. However, as a fundamental component in this cascade, Wnt3 has not been well understood for the expression level and pathogenic mechanism in gastric carcinogenesis. Here, this research was undertaken to elucidate the important role of Wnt3 in gastric cancer. Wnt3 expression in gastric carcinomas and their respective normal tissues was examined by immunoblotting and immunohistochemistry. In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues. Knocking down Wnt3 in MGC-803 gastric cancer cells by small interfering RNAs transfection led to an obvious decrease in both transcript and protein levels. Silence of Wnt3 expression in gastric cancer cells inhibited the expression of β-catenin and cyclin D1 genes in Wnt/β-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate. Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer.

No MeSH data available.


Related in: MedlinePlus