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Cooperatively transcriptional and epigenetic regulation of sonic hedgehog overexpression drives malignant potential of breast cancer.

Duan ZH, Wang HC, Zhao DM, Ji XX, Song M, Yang XJ, Cui W - Cancer Sci. (2015)

Bottom Line: Comprehensive understanding of the regulation mechanism of Shh in cancer cells is necessary to find an effective approach to selectively block its tumorigenic function.Moreover, in vitro data demonstrated that both NF-κB activation and hypomethylation in promoter region were positively associated with the overexpression of Shh.Furthermore, the biological function data indicated that overexpressed Shh enhanced the self-renewal capacity and migration ability of breast cancer cells, which could be augmented by promoter demethylation and NF-κB activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, College of Life Science and Biopharmaceutical of Shenyang Pharmaceutical University, Shenyang, China.

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Sonic hedgehog (Shh) expression, nuclear factor-kappa B (NF-κB) expression and promoter hypomethylation in breast cancer. (a) The expression of Shh and NF-κB, and methylation status of Shh promoter in representative breast cancer tissues. M, methylation; UM, unmethylation. Figures magnified 200× or 400×. (b) The correlation among Shh, NF-κB and promoter methylation in breast cancer. A sample is defined as Shh or NF-κB + if it has an IS ≥4. (c) Overall survival according to expression of Shh in breast cancer.
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fig01: Sonic hedgehog (Shh) expression, nuclear factor-kappa B (NF-κB) expression and promoter hypomethylation in breast cancer. (a) The expression of Shh and NF-κB, and methylation status of Shh promoter in representative breast cancer tissues. M, methylation; UM, unmethylation. Figures magnified 200× or 400×. (b) The correlation among Shh, NF-κB and promoter methylation in breast cancer. A sample is defined as Shh or NF-κB + if it has an IS ≥4. (c) Overall survival according to expression of Shh in breast cancer.

Mentions: To explore the correlation among Shh, NF-κB and promoter methylation in breast cancer, we detected the expression of Shh and NF-κB using the immunohistochemistry method, and measured the promoter methylation status of Shh using MS-PCR. Our data showed that the level of Shh was higher in tissues with positive NF-κB nuclear staining and promoter hypomethylation, whereas the level of Shh was lower in tissues with negative NF-κB nuclear staining and promoter hypermethylation (see Fig1a). In detail, the rate of positive Shh expression was 87.1% in tissues with positive NF-κB nuclear staining and promoter hypomethylation, but 28.6% in tissues with negative NF-κB nuclear staining and promoter hypermethylation (see Fig1b). Statistical analysis data indicated a significant difference among methylation (−)/NF-κB (+), methylation (+)/NF-κB (−), methylation (−)/NF-κB (−) and methylation (+)/NF-κB (+) in Shh expression level (see Fig.1b), suggesting a crucial role of the hypomethylation along with NF-κB activation in the regulation of Shh expression.


Cooperatively transcriptional and epigenetic regulation of sonic hedgehog overexpression drives malignant potential of breast cancer.

Duan ZH, Wang HC, Zhao DM, Ji XX, Song M, Yang XJ, Cui W - Cancer Sci. (2015)

Sonic hedgehog (Shh) expression, nuclear factor-kappa B (NF-κB) expression and promoter hypomethylation in breast cancer. (a) The expression of Shh and NF-κB, and methylation status of Shh promoter in representative breast cancer tissues. M, methylation; UM, unmethylation. Figures magnified 200× or 400×. (b) The correlation among Shh, NF-κB and promoter methylation in breast cancer. A sample is defined as Shh or NF-κB + if it has an IS ≥4. (c) Overall survival according to expression of Shh in breast cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556399&req=5

fig01: Sonic hedgehog (Shh) expression, nuclear factor-kappa B (NF-κB) expression and promoter hypomethylation in breast cancer. (a) The expression of Shh and NF-κB, and methylation status of Shh promoter in representative breast cancer tissues. M, methylation; UM, unmethylation. Figures magnified 200× or 400×. (b) The correlation among Shh, NF-κB and promoter methylation in breast cancer. A sample is defined as Shh or NF-κB + if it has an IS ≥4. (c) Overall survival according to expression of Shh in breast cancer.
Mentions: To explore the correlation among Shh, NF-κB and promoter methylation in breast cancer, we detected the expression of Shh and NF-κB using the immunohistochemistry method, and measured the promoter methylation status of Shh using MS-PCR. Our data showed that the level of Shh was higher in tissues with positive NF-κB nuclear staining and promoter hypomethylation, whereas the level of Shh was lower in tissues with negative NF-κB nuclear staining and promoter hypermethylation (see Fig1a). In detail, the rate of positive Shh expression was 87.1% in tissues with positive NF-κB nuclear staining and promoter hypomethylation, but 28.6% in tissues with negative NF-κB nuclear staining and promoter hypermethylation (see Fig1b). Statistical analysis data indicated a significant difference among methylation (−)/NF-κB (+), methylation (+)/NF-κB (−), methylation (−)/NF-κB (−) and methylation (+)/NF-κB (+) in Shh expression level (see Fig.1b), suggesting a crucial role of the hypomethylation along with NF-κB activation in the regulation of Shh expression.

Bottom Line: Comprehensive understanding of the regulation mechanism of Shh in cancer cells is necessary to find an effective approach to selectively block its tumorigenic function.Moreover, in vitro data demonstrated that both NF-κB activation and hypomethylation in promoter region were positively associated with the overexpression of Shh.Furthermore, the biological function data indicated that overexpressed Shh enhanced the self-renewal capacity and migration ability of breast cancer cells, which could be augmented by promoter demethylation and NF-κB activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, College of Life Science and Biopharmaceutical of Shenyang Pharmaceutical University, Shenyang, China.

Show MeSH
Related in: MedlinePlus