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Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-α cleavage by ADAM17

Authors
 Ming-Qing Gao ; Baek Gil Kim ; Nam Hoon Cho ; Joo-Heon Yoon ; Yoon Pyo Choi ; Suki Kang 
Citation
 Cancer Letters, Vol.336(1) : 240~246, 2013 
Journal Title
 Cancer Letters 
ISSN
 0304-3835 
Issue Date
2013
Abstract
We demonstrate here increased expression of ADAM17 protein in cancer-associated fibroblasts (CAFs) extracted from human breast carcinomas compared with donor-matched normal fibroblasts, and TGF-α secretion positively correlates with ADAM17 expression in these cells. In SK-BR-3 cells co-cultured with CAFs, CAF-secreted TGF-α promotes cell proliferation by activation of EGFR, Akt, and ERK, but it does not promote cell migration. Furthermore, anti-TGF-α neutralizing antibodies antagonize the CAF-dependent increase in proliferation and activation of EGFR, Akt and ERK. Thus, pharmacologic inhibition of ADAM17 and TGF-α may have therapeutic potential for the treatment of breast cancer when fibroblast-directed therapy is considered.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/87065
DOI
10.1016/j.canlet.2013.05.011
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
1. 연구논문 > 1. College of Medicine > Dept. of Otorhinolaryngology
1. 연구논문 > 1. College of Medicine > Dept. of Pathology
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0304383513003807
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