Details

Autor(en) / Beteiligte

• Nie, Fang
• Yang, Jian
• Wen, Song
• An, Yan‐Li
• Ding, Jie
• Ju, Sheng‐Hong
• Zhao, Zhen
• Chen, Hua‐Jun
• Peng, Xin‐Gui
• Wong, Stephen T. C.
• Zhao, Hong
• Teng, Gao‐Jun

Titel

Involvement of epidermal growth factor receptor overexpression in the promotion of breast cancer brain metastasis

Ist Teil von

• Cancer, 2012-11, Vol.118 (21), p.5198-5209

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• BACKGROUND: Brain‐metastatic breast cancer (BMBC) is increasing and poses a severe clinical problem because of the lack of effective treatments and because the underlying molecular mechanisms are largely unknown. Recent work has demonstrated that deregulation of epidermal growth factor receptor (EGFR) may correlate with BMBC progression. However, the exact contribution that EGFR makes to BMBC remains unclear. METHODS: The role of EGFR in BMBC was explored by serial analyses in a brain‐trophic clone of human MDA‐MB‐231 breast carcinoma cells (231‐BR cells). EGFR expression was inhibited by stable short‐hairpin RNA transfection or by the kinase inhibitor erlotinib, and it was activated by heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF). Cell growth and invasion activities also were analyzed in vitro and in vivo. RESULTS: EGFR inhibition or activation strongly affected 231‐BR cell migration/invasion activities as assessed by an adhesion assay, a wound‐healing assay, a Boyden chamber invasion assay, and cytoskeleton staining. Also, EGFR inhibition significantly decreased brain metastases of 231‐BR cells in vivo. Surprisingly, changes to EGFR expression affected cell proliferation activities less significantly as determined by a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, an anchorage‐independent growth assay, and cell cycle analysis. Immunoblot analysis suggested that EGFR drives cells' invasiveness capability mainly through phosphoinositide 3‐kinase/protein kinase B and phospholipase C γ downstream pathways. In addition, EGFR was involved less in proliferation because of the insensitivity of the downstream mitogen‐activated protein kinase pathway. CONCLUSIONS: The current results indicated that EGFR plays more important roles in cell migration and invasion to the brain than in cell proliferation progression on 231‐BR cells, providing new evidence of the potential value of EGFR inhibition in treating BMBC. Cancer 2012. © 2012 American Cancer Society. Epidermal growth factor receptor (EGFR) plays more important roles in cell migration and invasion to the brain than it plays in cell proliferation progression in breast cancer brain‐seeking cells. The current findings provide new evidence of the potential value of EGFR inhibition in treating brain‐metastatic breast cancer.