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Secreted frizzled‑related protein 2 is epigenetically silenced and functions as a tumor suppressor in oral squamous cell carcinoma.

Xiao C, Wang L, Zhu L, Zhang C, Zhou J - Mol Med Rep (2014)

Bottom Line: In addition, the loss of SFRP2 expression was associated with hypermethylation of its promoter.Mechanistic investigations revealed that SFRP2 inhibited the development of OSCC in vitro and in vivo through an increase in the expression levels of glycogen synthase kinase‑3β and a decrease in the expression level of cyclin D1, a direct read‑out gene of active Wnt signaling.Further studies on the precise mechanisms underlying the inhibition of Wnt signaling by SFRP2 and its association with β‑catenin are required.

View Article: PubMed Central - PubMed

Affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.

ABSTRACT
The role of epigenetic inactivation of secreted frizzled‑related protein 2 (SFRP2) and its functions in the development of oral squamous cell carcinoma (OSCC) remain to be elucidated. The present study demonstrated that SFRP2 mRNA was detected in 97.96% of tumor‑adjacent normal tissues, while its expression was only detected in 16.33% of the tumor samples. In addition, the loss of SFRP2 expression was associated with hypermethylation of its promoter. As expected, the overexpression of SFRP2 in OSCC cell lines (Tca8113) suppressed cell proliferation and arrested the cell cycle in the G1 phase. Overexpression of SFRP2 also effectively repressed tumor growth in xenograft animals. Mechanistic investigations revealed that SFRP2 inhibited the development of OSCC in vitro and in vivo through an increase in the expression levels of glycogen synthase kinase‑3β and a decrease in the expression level of cyclin D1, a direct read‑out gene of active Wnt signaling. In addition, an increase in the expression of β‑catenin was observed in the Tca8113/SFRP2 cells and in the animal models overexpressing SFRP2. Therefore, the results of the present study provide insight into the role of SFRP2 as a functional tumor suppressor in the development of OSCC through inhibition of the Wnt signaling pathway. Further studies on the precise mechanisms underlying the inhibition of Wnt signaling by SFRP2 and its association with β‑catenin are required.

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Immunohistochemical analysis of the expression levels of cyclin D1, glycogen synthase kinase-3β and β-catenin in representative samples from the animals inoculated with Tca8113/pcDNA3.1 and Tca8113/SFRP2 cells (stained by 3,3′-diaminobenzidine). (A, C and E) Tissues from the group of animals inoculated with Tca8113/pcDNA3.1. (B, D and F) Tissues from the group of animals inoculated with Tca8113/SFRP2. (magnification, ×200). SFRP2, secreted frizzled-related protein 2.
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f4-mmr-10-05-2293: Immunohistochemical analysis of the expression levels of cyclin D1, glycogen synthase kinase-3β and β-catenin in representative samples from the animals inoculated with Tca8113/pcDNA3.1 and Tca8113/SFRP2 cells (stained by 3,3′-diaminobenzidine). (A, C and E) Tissues from the group of animals inoculated with Tca8113/pcDNA3.1. (B, D and F) Tissues from the group of animals inoculated with Tca8113/SFRP2. (magnification, ×200). SFRP2, secreted frizzled-related protein 2.

Mentions: In order to investigate whether SFRP2 affects the growth of OSCC via the Wnt signaling pathway in nude mice, the expression levels of GSK-3β, β-catenin and cyclin D1 in tumor tissues were further analyzed by immunohistochemical analysis. Compared with the animals in the Tca8113/pcDNA3.1 group, the expression level of cyclin D1 was markedly decreased (Fig. 4), while the expression levels of GSK-3β and β-catenin was significantly increased in the cell cytoplasm and cell membrane in the animals from the Tca8113/SFRP2 group (Fig. 4).


Secreted frizzled‑related protein 2 is epigenetically silenced and functions as a tumor suppressor in oral squamous cell carcinoma.

Xiao C, Wang L, Zhu L, Zhang C, Zhou J - Mol Med Rep (2014)

Immunohistochemical analysis of the expression levels of cyclin D1, glycogen synthase kinase-3β and β-catenin in representative samples from the animals inoculated with Tca8113/pcDNA3.1 and Tca8113/SFRP2 cells (stained by 3,3′-diaminobenzidine). (A, C and E) Tissues from the group of animals inoculated with Tca8113/pcDNA3.1. (B, D and F) Tissues from the group of animals inoculated with Tca8113/SFRP2. (magnification, ×200). SFRP2, secreted frizzled-related protein 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214353&req=5

f4-mmr-10-05-2293: Immunohistochemical analysis of the expression levels of cyclin D1, glycogen synthase kinase-3β and β-catenin in representative samples from the animals inoculated with Tca8113/pcDNA3.1 and Tca8113/SFRP2 cells (stained by 3,3′-diaminobenzidine). (A, C and E) Tissues from the group of animals inoculated with Tca8113/pcDNA3.1. (B, D and F) Tissues from the group of animals inoculated with Tca8113/SFRP2. (magnification, ×200). SFRP2, secreted frizzled-related protein 2.
Mentions: In order to investigate whether SFRP2 affects the growth of OSCC via the Wnt signaling pathway in nude mice, the expression levels of GSK-3β, β-catenin and cyclin D1 in tumor tissues were further analyzed by immunohistochemical analysis. Compared with the animals in the Tca8113/pcDNA3.1 group, the expression level of cyclin D1 was markedly decreased (Fig. 4), while the expression levels of GSK-3β and β-catenin was significantly increased in the cell cytoplasm and cell membrane in the animals from the Tca8113/SFRP2 group (Fig. 4).

Bottom Line: In addition, the loss of SFRP2 expression was associated with hypermethylation of its promoter.Mechanistic investigations revealed that SFRP2 inhibited the development of OSCC in vitro and in vivo through an increase in the expression levels of glycogen synthase kinase‑3β and a decrease in the expression level of cyclin D1, a direct read‑out gene of active Wnt signaling.Further studies on the precise mechanisms underlying the inhibition of Wnt signaling by SFRP2 and its association with β‑catenin are required.

View Article: PubMed Central - PubMed

Affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.

ABSTRACT
The role of epigenetic inactivation of secreted frizzled‑related protein 2 (SFRP2) and its functions in the development of oral squamous cell carcinoma (OSCC) remain to be elucidated. The present study demonstrated that SFRP2 mRNA was detected in 97.96% of tumor‑adjacent normal tissues, while its expression was only detected in 16.33% of the tumor samples. In addition, the loss of SFRP2 expression was associated with hypermethylation of its promoter. As expected, the overexpression of SFRP2 in OSCC cell lines (Tca8113) suppressed cell proliferation and arrested the cell cycle in the G1 phase. Overexpression of SFRP2 also effectively repressed tumor growth in xenograft animals. Mechanistic investigations revealed that SFRP2 inhibited the development of OSCC in vitro and in vivo through an increase in the expression levels of glycogen synthase kinase‑3β and a decrease in the expression level of cyclin D1, a direct read‑out gene of active Wnt signaling. In addition, an increase in the expression of β‑catenin was observed in the Tca8113/SFRP2 cells and in the animal models overexpressing SFRP2. Therefore, the results of the present study provide insight into the role of SFRP2 as a functional tumor suppressor in the development of OSCC through inhibition of the Wnt signaling pathway. Further studies on the precise mechanisms underlying the inhibition of Wnt signaling by SFRP2 and its association with β‑catenin are required.

Show MeSH
Related in: MedlinePlus