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. 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 TGFbeta, Hedgehog, cell adhesion, and p63 required for myoepithelial cell differentiation, the elimination of which resulted in loss of myoepithelial cells and progression to invasion.
Hu
Min
M
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Yao
Jun
J
Carroll
Danielle K
DK
Weremowicz
Stanislawa
S
Chen
Haiyan
H
Carrasco
Daniel
D
Richardson
Andrea
A
Violette
Shelia
S
Nikolskaya
Tatiana
T
Nikolsky
Yuri
Y
Bauerlein
Erica L
EL
Hahn
William C
WC
Gelman
Rebecca S
RS
Allred
Craig
C
Bissell
Mina J
MJ
Schnitt
Stuart
S
Polyak
Kornelia
K
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006801:Humans; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D016212:Transforming Growth Factor beta / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53