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ToolsDawoud, Marwa M., Jones, Dylan T., Chelala, Claude, Abdou, Asmaa G., Dreger, Sally A., Asaad, Nancy, Abd El-Wahed, Moshirah and Jones, Louise (2022) Expression profile of myoepithelial cells in DCIS: Do they change from protective angels to wicked witches? Applied Immunohistochemistry and Molecular Morphology, 30 (6). pp. 397-409. ISSN 1541-2016
Full text not available from this repository. (Request a copy)Abstract
The mechanism of transition of ductal carcinoma in situ (DCIS) to invasive cancer is elusive but recently changes in the myoepithelial cells (MECs) have been implicated. The aim of this study is to investigate the changes in gene profile of MECs in DCIS that could compromise their tumor suppressor function leading to promotion of tumor progression. Immuno-laser capture microdissection (LCM) was used to isolate MECs from normal and DCIS breast tissues followed by whole genome expression profiling using Affymetrix HGU-133 plus2.0 arrays. The data were analyzed using Bioconductor packages then validated by using real-time quantitative polymerase chain reaction and immunohistochemistry. Ingenuity Pathways software analysis showed clustering of most of the altered genes in cancer and cell death networks, with the Wnt/B-catenin pathway as the top canonical pathway. Validation revealed a 71.4% correlation rate with the array results. Most dramatic was upregulation of Fibronectin 1 (FN1) in DCIS-associated MECs. Immunohistochemistry analysis for FN1 on normal and DCIS tissues confirmed a strong correlation between FN1 protein expression by MECs and DCIS (P<0.0001) and between high expression level and presence of invasion (P=0.006) in DCIS. Other validated alterations in MEC expression profile included upregulation of Nephronectin and downregulation of parathyroid hormone like hormone (PTHLH), fibroblast growth factor receptor 2 (FGFR2), ADAMTS5, TGFBR3, and CAV1. In vitro experiments revealed downregulation of PTHLH in DCIS-modified MECs versus normal lines when cultured on Fibronectin matrix. This is the first study to use this in vivo technique to investigate molecular changes in MECs in DCIS. This study adds more evidences to the molecular deviations in MECs toward tumor progression in DCIS through upregulation of the tumor-promoting molecules that may lead to novel predictive and therapeutic targets.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This study was funded by the Egyptian government. Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved. |
| Uncontrolled Keywords: | ductal carcinoma in situ,fn1,immuno-laser capture microdissection,myoepithelial cells,pthlh,whole genome expression profiling,pathology and forensic medicine,histology,medical laboratory technology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2734 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 03 Dec 2024 01:35 |
| Last Modified: | 03 Dec 2024 01:35 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97859 |
| DOI: | 10.1097/PAI.0000000000001028 |
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