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- W4361261475 abstract "<div>Abstract<p>Human epidermal growth factor receptor 2 (HER2) overexpression stimulates cell growth in <i>p53</i>-mutated cells while it inhibits cell proliferation in those with wild-type <i>p53</i>, but the molecular mechanism is unknown. The <i>Dmp1</i> promoter was activated by HER2/neu through the phosphatidylinositol-3′-kinase-Akt-NF-κB pathway, which in turn stimulated <i>Arf</i> transcription. Binding of p65 and p52 subunits of NF-κB was shown to the <i>Dmp1</i> promoter and that of Dmp1 to the <i>Arf</i> promoter on HER2/neu overexpression. Both Dmp1 and p53 were induced in premalignant lesions from mouse mammary tumor virus-<i>neu</i> mice, and mammary tumorigenesis was significantly accelerated in both <i>Dmp1<sup>+/−</sup></i> and <i>Dmp1</i><sup>−/−</sup> mice. Selective deletion of <i>Dmp1</i> and/or overexpression of Tbx2/Pokemon was found in >50% of wild-type HER2/neu carcinomas, although the involvement of Arf, Mdm2, or p53 was rare. Tumors from <i>Dmp1<sup>+/−</sup>, Dmp1</i><sup>−/−</sup>, and wild-type <i>neu</i> mice with hemizygous <i>Dmp1</i> deletion showed significant downregulation of <i>Arf</i> and <i>p21<sup>Cip1/WAF1</sup></i>, showing p53 inactivity and more aggressive phenotypes than tumors without <i>Dmp1</i> deletion. Notably, endogenous h<i>DMP1</i> mRNA decreased when <i>HER2</i> was depleted in human breast cancer cells. Our study shows the pivotal roles of Dmp1 in HER2/neu-p53 signaling and breast carcinogenesis. Cancer Res; 70(22); 9084–94. ©2010 AACR.</p></div>" @default.
- W4361261475 created "2023-03-31" @default.
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- W4361261475 date "2023-03-30" @default.
- W4361261475 modified "2023-09-25" @default.
- W4361261475 title "Data from Critical Roles of DMP1 in Human Epidermal Growth Factor Receptor 2/neu-Arf-p53 Signaling and Breast Cancer Development" @default.
- W4361261475 doi "https://doi.org/10.1158/0008-5472.c.6500870.v1" @default.
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