Journal
ONCOTARGET
Volume 6, Issue 5, Pages 2604-2614Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3094
Keywords
MET mutations; Breast Cancer; Malignant transformation
Categories
Funding
- Komen for the Cure [SAC 100004]
- American Cancer Society [121329-RSG-11-187-01-TBG]
- Commonwealth Foundation for Cancer Research
- Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (IPCT)
- Sheikh Khalifa Foundation
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Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials.
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