Le Miroir des sports : publication hebdomadaire illustrée

14 mai 19351935/05/14 (N824)-1935/05/14

Mechanistic Linkage Between Aurora-A Over-expression, SMAD5 Activation And ERα Down-Regulation In Initially ERα+ Breast Cancer Cells.

<p>(A) Immunoblot analysis showing p∼Aurora-A in breast cancer cells. (B) Immunofluorescence analysis showing that Aurora-A-induced ERα down-regulation is linked to p∼SMAD5 nuclear activation. ERα (Abcam, Cambridge, Massachusetts, USA) was labeled in green, p∼SMAD5 (Cell Signaling Technology, Boston, MA, USA) was labeled in red and nuclei were labeled in blue with DAPI. (C) Graph showing the percentage of cells expressing ERα and p∼SMAD5 in breast cancer cells. Experiments were performed in triplicate (+/− s.d.; *p<0.0083 vs. vMCF-7^{ΔRaf-1/Aurora-A}; **p<0.0048 vs. vMCF-7^{ΔRaf-1/Aurora-A}; ***p<0.0083 vs. vMCF-7^{ΔRaf-1/Aurora-A}; ****p<0.0021 vs. vMCF-7^{ΔRaf-1/Aurora-A}).</p

Model of endocrine resistance and breast cancer progression.

<p>Aberrant activation of MAPK signaling stabilizes and activates Aurora-A kinase that in turn induces down-regulation/loss of ERα expression through phosphorylation and activation of SMAD5 nuclear signaling leading to endocrine resistance and tumor progression.</p

Endocrine Resistant Breast Cancer Cells.

<p>(<b>A</b>) Immumohistochemistry staining of low-grade tubular tumors for MCF-7 and high-grade vMCF-7^ΔRaf-1 Primary and Metastatic tumors. Breast cancer xenografts were stained with a polyclonal antibody targeting the ERα (Abcam, Cambridge, Massachusetts, USA). (<b>B</b>) Immunofluorescence analysis showing down-regulation of ERα expression in vMCF-7^ΔRaf-1 1GX cancer cells compared to parental MCF-7 and vMCF-7^ΔRaf-1 cells. (<b>C</b>) Graph showing the percentage of cancer cells harboring an ERα^low/− phenotype from three independent experiments (+/− s.d.; *p<0.0705 vs. MCF-7; **p<0.0001 vs. vMCF-7^ΔRaf-1). (<b>D</b>) Graph showing the percentage of cancer cells in the S phase of the cell cycle during starvation from 17-β estradiol and following treatment with 17-β estradiol (10⁻¹⁰ M) alone or in combination with 4-OH-tamoxifen (10⁻⁷ M) for 48 hours from three independent experiments (+/− s.d.; *p<0.0008 vs. MCF-7; **p<0.0009 vs. vMCF-7^ΔRaf-1).</p

Role Of SMAD5 Over-Expression In ERα Down-Regulation.

<p>(<b>A</b>) Immunoblot analysis showing parental and MCF-7 cells engineered to over-express SMAD5. (<b>B</b>) Immunofluorescence analysis showing that SMAD5 over-expression induces ERα down-regulation in ERα+MCF-7 cells. ERα (Abcam, Cambridge, Massachusetts, USA) was labeled in green, p∼SMAD5 (Cell Signaling Technology, Boston, MA, USA) was labeled in red and nuclei were labeled in blue with DAPI. (<b>C</b>) Graph showing the percentage of cells expressing p∼SMAD5 and ERα in vMCF-7^SMAD5 and parental cells. Experiments were performed in triplicate (+/− s.d.; *p<0.0001 vs. MCF-7; **p<0.0001 vs. MCF-7).</p

Additional file 1: Table S1. of Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients

Select patient and clinical characteristics of women included in this study as well as the relationship between the number of CD68-positive macrophages and number of CLS (per unit area of fat) and hormones. (DOCX 25 kb