PMID- 25962646 OWN - NLM STAT- MEDLINE DCOM- 20160211 LR - 20181202 IS - 1944-446X (Electronic) IS - 1000-467X (Print) IS - 1944-446X (Linking) VI - 34 IP - 3 DP - 2015 Mar 5 TI - Epithelial cell identity in hyperplastic precursors of breast cancer. PG - 121-9 LID - 10.1186/s40880-015-0004-z [doi] LID - 3 AB - 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. METHODS: 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. RESULTS: 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. FAU - Coradini, Danila AU - Coradini D AD - Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan, 20133, Italy. danila.coradini@gmail.com. FAU - Boracchi, Patrizia AU - Boracchi P AD - Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan, 20133, Italy. patrizia.boracchi@unimi.it. FAU - Oriana, Saro AU - Oriana S AD - Senology Center, Ambrosiana Clinic, Cesano Boscone, Milan, 20090, Italy. saroriana@hotmail.it. FAU - Biganzoli, Elia AU - Biganzoli E AD - Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan, 20133, Italy. elia.biganzoli@unimi.it. FAU - Ambrogi, Federico AU - Ambrogi F AD - Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan, 20133, Italy. federico.ambrogi@unimi.it. LA - eng PT - Journal Article DEP - 20150305 PL - England TA - Chin J Cancer JT - Chinese journal of cancer JID - 101498232 RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogens) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) SB - IM MH - Adipose Tissue MH - Adult MH - Breast MH - *Breast Neoplasms MH - Carcinoma in Situ MH - Carcinoma, Intraductal, Noninfiltrating MH - *Cell Proliferation MH - *Cell Transformation, Neoplastic MH - Epithelial Cells MH - Estrogen Receptor alpha MH - Estrogens MH - Humans MH - Hyperplasia MH - Mammary Glands, Human MH - *Receptors, Estrogen MH - Receptors, Progesterone PMC - PMC4593345 EDAT- 2015/05/13 06:00 MHDA- 2016/02/13 06:00 PMCR- 2015/03/05 CRDT- 2015/05/13 06:00 PHST- 2014/05/05 00:00 [received] PHST- 2014/11/26 00:00 [accepted] PHST- 2015/05/13 06:00 [entrez] PHST- 2015/05/13 06:00 [pubmed] PHST- 2016/02/13 06:00 [medline] PHST- 2015/03/05 00:00 [pmc-release] AID - 10.1186/s40880-015-0004-z [pii] AID - 4 [pii] AID - 10.1186/s40880-015-0004-z [doi] PST - epublish SO - Chin J Cancer. 2015 Mar 5;34(3):121-9. doi: 10.1186/s40880-015-0004-z.