| Description |
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Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase
inhibitors (TKIs) have shown clinical efficacy in lung, colon, and pancreatic
cancers. In lung cancer, resistance to EGFR TKIs correlates with amplification of the
hepatocyte growth factor (HGF) receptor tyrosine kinase Met. Breast cancers do not
respond to EGFR TKIs, ... read moreeven though EGFR is overexpressed. This intrinsic resistance to
EGFR TKIs in breast cancer does not correlate with Met amplification. In several
tissue monoculture models of human breast cancer, Met, although expressed, is not
phosphorylated, suggesting a requirement for a paracrine-produced ligand. In fact,
HGF, the ligand for Met, is not expressed in epithelial cells but is secreted by
fibroblasts in the tumor stroma. We have identified a number of breast cancer cell
lines that are sensitive to EGFR TKIs. This sensitivity is in conflict with the
observed clinical resistance to EGFR TKIs in breast cancers. Here we demonstrate that
fibroblast secretion of HGF activates Met and leads to EGFR/Met crosstalk and
resistance to EGFR TKIs in triple-negative breast cancer (TNBC).
Keywords: bovine serum albumin, Dulbecco's modified Eagle's medium,
epidermal growth factor receptor, enzyme-linked immunosorbent assay, hepatocyte
growth factor, phosphate-buffered saline, reduction mammoplasty fibroblasts
expressing human hepatocyte growth factor, small hairpin RNA, tyrosine kinase
inhibitor, triple-negative breast cancer.
Springer Open.read less
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| Citation |
- Mueller, Kelly, Julie M. Madden, Gina L. Zoratti, Charlotte
Kuperwasser, Karin List, and Julie L. Boerner. "Fibroblast-secreted hepatocyte growth
factor mediates epidermal growth factor receptor tyrosine kinase inhibitor resistance
in triple-negative breast cancers through paracrine activation of Met." Breast Cancer
Research 14, no. 6 (8, 2012): 1-11.
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