Regulation of In Situ to Invasive Breast Carcinoma Transition

The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a poorly understood key event in breast tumor progression. Here, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a model of human DCIS and primary breast tumors. Prog...

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Bibliographic Details
Published in:Cancer cell 2008-05, Vol.13 (5), p.394-406
Main Authors: Hu, Min, Yao, Jun, Carroll, Danielle K., Weremowicz, Stanislawa, Chen, Haiyan, Carrasco, Daniel, Richardson, Andrea, Violette, Shelia, Nikolskaya, Tatiana, Nikolsky, Yuri, Bauerlein, Erica L., Hahn, William C., Gelman, Rebecca S., Allred, Craig, Bissell, Mina J., Schnitt, Stuart, Polyak, Kornelia
Format: Article
Language:English
Subjects:
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Carcinoma, Intraductal, Noninfiltrating - genetics
Carcinoma, Intraductal, Noninfiltrating - pathology
Cell Adhesion
CELLBIO
CELLCYCLE
DNA Methylation
Female
Gene Expression Regulation, Neoplastic
Homeostasis
Humans
Neoplasm Invasiveness
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Transforming Growth Factor beta - genetics
Tumor Suppressor Protein p53 - genetics
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Summary:The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a poorly understood key event in breast tumor progression. Here, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a model of human DCIS and primary breast tumors. Progression to invasion was promoted by fibroblasts and inhibited by normal myoepithelial cells. Molecular profiles of isolated luminal epithelial and myoepithelial cells identified an intricate interaction network involving TGFβ, Hedgehog, cell adhesion, and p63 required for myoepithelial cell differentiation, the elimination of which resulted in loss of myoepithelial cells and progression to invasion.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2008.03.007