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Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β.
- Source :
-
Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2018 Jan; Vol. 98 (1), pp. 117-129. Date of Electronic Publication: 2017 Oct 16. - Publication Year :
- 2018
-
Abstract
- Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated. Human BC cell lines served as functional models to study siRNA-mediated inhibition of AP-2β. The normal mammary gland epithelium showed scattered AP-2β-positive cells in the luminal cell layer. Various reactive and pre-invasive neoplastic lesions, including apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ (LCIS) showed enhanced AP-2β expression. Cases of ductal carcinoma in situ (DCIS) were more often AP-2β-negative (P<0.001). In invasive BC cohorts, AP-2β-positivity was associated with the lobular BC subtype (P<0.001), loss of E-cadherin (P<0.001), a positive estrogen receptor (ER) status (P<0.001), low Ki67 (P<0.001), low/intermediate Oncotype DX recurrence scores (P<0.001), and prolonged event-free survival (P=0.003). BCs from GEM models were all AP-2β-negative. In human BC cell lines, AP-2β expression was independent from ER-signaling. SiRNA-mediated inhibition of AP-2β diminished proliferation of lobular BC cell lines in vitro. In summary, AP-2β is a new mammary epithelial differentiation marker. Its expression is preferentially retained and enhanced in LCIS and invasive lobular BC and has prognostic implications. Our findings indicate that AP-2β controls tumor cell proliferation in this slow-growing BC subtype.
- Subjects :
- Animals
Biomarkers, Tumor metabolism
Breast Carcinoma In Situ pathology
Breast Carcinoma In Situ surgery
Breast Neoplasms blood
Breast Neoplasms pathology
Breast Neoplasms surgery
Carcinoma, Lobular pathology
Carcinoma, Lobular surgery
Cell Line, Tumor
Cell Proliferation
Cohort Studies
Disease-Free Survival
Female
Follow-Up Studies
Humans
Mammary Glands, Human pathology
Mammary Glands, Human surgery
Mice, Transgenic
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Proteins genetics
Progression-Free Survival
RNA Interference
Transcription Factor AP-2 antagonists & inhibitors
Transcription Factor AP-2 chemistry
Transcription Factor AP-2 genetics
Breast Carcinoma In Situ metabolism
Breast Neoplasms metabolism
Carcinoma, Lobular metabolism
Gene Expression Regulation, Neoplastic
Mammary Glands, Human metabolism
Neoplasm Proteins metabolism
Transcription Factor AP-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0307
- Volume :
- 98
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Laboratory investigation; a journal of technical methods and pathology
- Publication Type :
- Academic Journal
- Accession number :
- 29035379
- Full Text :
- https://doi.org/10.1038/labinvest.2017.106