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Differential Expression of the Genes Coding for Adipokines and Epithelial Cell Polarity Components in Women With Low and High Mammographic Density

  • Danila Coradini
    Correspondence
    Address for correspondence: Danila Coradini, Laboratory of Medical Statistics and Biometry, “Giulio A. Maccacaro,” Department of Clinical Sciences and Community Health, University of Milan, Campus Cascina Rosa, Milan, Italy.
    Affiliations
    Laboratory of Medical Statistics and Biometry, “Giulio A. Maccacaro,” Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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  • Federico Ambrogi
    Affiliations
    Laboratory of Medical Statistics and Biometry, “Giulio A. Maccacaro,” Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Scientific Directorate, IRCCS Policlinico San Donato, San Donato Milanese, Italy
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      Highlights

      • Dense breast tissue is likely associated with a high risk of cancer development.
      • Nonfatty stroma is proposed as the responsible for epithelial cells transformation.
      • The tissue levels of some adipokines can adversely affect epithelial cell polarity.
      • Leptin could mediate the stroma-epithelium interaction promoting cell transformation.

      Abstract

      Background

      Women with extensive mammographic density (MD) are more likely to develop breast cancer than women with low MD because of a high epithelial component associated with a high proportion of stromal cells. To elucidate the biological association between high MD and risk of breast cancer, we compared the expression of a panel of genes coding for leptin, adiponectin, and some component of cell polarity and adherens junction complexes in dense and non-dense breast tissue.

      Methods

      We interrogated a public dataset composed by 120 specimens of normal breast tissue with MD evaluation. The differential expression of the selected genes in the 2 MD subgroups was assessed by the Wilcoxon test, whereas Kruskal-Wallis test evaluated the differential expression of single genes in the fatty, epithelium, or nonfatty compartment. Spearman's correlation measured the relationship among genes in the subset with the highest epithelium proportion.

      Results

      In high MD, the expression level of PARD6B, CRB3, PATJ, LLGL2, CDH1, and MARVELD2 significantly lowered in tissues with the highest epithelium proportion, whereas, in low MD, the expression level of the genes increased with the increasing of the epithelium proportion. In the low MD subgroup, LEP correlated negatively with PRKCZ and DLG3, whereas, in high MD, such correlation was not observed.

      Conclusions

      The expression of the genes governing cell polarity establishment and cell-cell adhesion assembly differed significantly in the epithelial component of dense and non-dense breasts. The correlation pattern between LEP and PRKCZ or DLG3 agrees with the role of leptin in cell polarity disruption.

      Keywords

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