[ Special series on Breast Cancer ]
doi: 10.1186/s40880-015-0004-z
Epithelial cell identity in hyperplastic precursors of breast cancer
Danila Coradini, Patrizia Boracchi, Saro Oriana, Elia Biganzoli and Federico Ambrogi
Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan 20133, Italy
[Abstract]
Introduction
In the adult human breast, hyperplastic enlarged lobular unit (HELU) and atypical ductal hyperplasia (ADH) are two common abnormalities that frequently coexist with ductal carcinoma in situ (DCIS). For this reason, they have been proposed as the early steps in a biological continuum toward breast cancer.
Method
We investigated in silico the expression of 369 genes experimentally recognized as involved in establishing and maintaining epithelial cell identity and mammary gland remodeling, in HELUs or ADHs with respect to the corresponding patient-matched normal tissue.
Resultss
Despite the common luminal origin, HELUs and ADHs proved to be characterized by distinct gene profiles that overlap for 5 genes only. While HELUs were associated with the overexpression of progesterone receptor (PGR), ADHs were characterized by the overexpression of estrogen receptor 1 (ESR1) coupled with the overexpression of some proliferation-associated genes.
Conclusions
This unexpected finding contradicts the notion that in differentiated luminal cells the expression of estrogen receptor (ER) is dissociated from cell proliferation and suggests that the establishing of an ER-dependent signaling is able to sustain cell proliferation in an autocrine manner as an early event in tumor initiation. Although clinical evidence indicates that only a fraction of HELUs and ADHs evolve to invasive cancer, present findings warn that exposure to synthetic progestins, frequently administered as hormone-replacement therapy, and estrogens, when abnormally produced by adipose cells and persistently present in the stroma surrounding the mammary gland, may cause these hyperplastic lesions.
Introduction
In the adult human breast, hyperplastic enlarged lobular unit (HELU) and atypical ductal hyperplasia (ADH) are two common abnormalities that frequently coexist with ductal carcinoma in situ (DCIS). For this reason, they have been proposed as the early steps in a biological continuum toward breast cancer.
Method
We investigated in silico the expression of 369 genes experimentally recognized as involved in establishing and maintaining epithelial cell identity and mammary gland remodeling, in HELUs or ADHs with respect to the corresponding patient-matched normal tissue.
Resultss
Despite the common luminal origin, HELUs and ADHs proved to be characterized by distinct gene profiles that overlap for 5 genes only. While HELUs were associated with the overexpression of progesterone receptor (PGR), ADHs were characterized by the overexpression of estrogen receptor 1 (ESR1) coupled with the overexpression of some proliferation-associated genes.
Conclusions
This unexpected finding contradicts the notion that in differentiated luminal cells the expression of estrogen receptor (ER) is dissociated from cell proliferation and suggests that the establishing of an ER-dependent signaling is able to sustain cell proliferation in an autocrine manner as an early event in tumor initiation. Although clinical evidence indicates that only a fraction of HELUs and ADHs evolve to invasive cancer, present findings warn that exposure to synthetic progestins, frequently administered as hormone-replacement therapy, and estrogens, when abnormally produced by adipose cells and persistently present in the stroma surrounding the mammary gland, may cause these hyperplastic lesions.
Chinese Journal of Cancer 2015, Volume: 34, Issue 3
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Danila Coradini, Patrizia Boracchi, Saro Oriana, Elia Biganzoli and Federico Ambrogi. Epithelial cell identity in hyperplastic precursors of breast cancer. Chin J Cancer. 2015, 34:3. doi:10.1186/s40880-015-0004-z
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[ Html full-text / Citation export] (BioMed Central)
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[ More articles of the special series on Breast Cancer ]
Cite this article
Danila Coradini, Patrizia Boracchi, Saro Oriana, Elia Biganzoli and Federico Ambrogi. Epithelial cell identity in hyperplastic precursors of breast cancer. Chin J Cancer. 2015, 34:3. doi:10.1186/s40880-015-0004-z
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