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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Article Info
Publication History
Published online: May 19, 2022
Accepted:
May 16,
2022
Received in revised form:
May 3,
2022
Received:
January 21,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
