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Figure 8 | Breast Cancer Research

Figure 8

From: Integrative analyses of gene expression and DNA methylation profiles in breast cancer cell line models of tamoxifen-resistance indicate a potential role of cells with stem-like properties

Figure 8

A possible mechanism implicated in tamoxifen resistance in the TAMRcell line model. While tamoxifen competitively binds with estrogen receptor (ER) and prevents binding between estradiol and ER, thereby blocking estrogen mitogenetic activity, CCND1 (cyclin D1) expression remains high due to direct activation mediated by SOX2 and/or by the Wnt/β-catenin pathway through attenuation of the suppression effect of other SOX gene family members on this pathway. Transforming growth factor beta (TGFβ) and Notch pathways are also implicated in activation of CCND1 (cyclin D1). Cyclin D1 interacts with pocket proteins (Rb, P105 and P130) and abrogates their suppressive effect on E2F. Finally, activated E2F accomplishes G1/S transition. By this mechanism, the cancer cells may bypass the blocked estrogen-mediated mitogenesis and maintain proliferation.

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Breast Cancer Research

ISSN: 1465-542X

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