Functional consequence of the MET-T1010I polymorphism in breast cancer

نویسندگان

  • Shuying Liu
  • Funda Meric-Bernstam
  • Napa Parinyanitikul
  • Bailiang Wang
  • Agda K. Eterovic
  • Xiaofeng Zheng
  • Mihai Gagea
  • Mariana Chavez-MacGregor
  • Naoto T. Ueno
  • Xiudong Lei
  • Wanding Zhou
  • Lakshmy Nair
  • Debu Tripathy
  • Powel H. Brown
  • Gabriel N. Hortobagyi
  • Ken Chen
  • John Mendelsohn
  • Gordon B. Mills
  • Ana M. Gonzalez-Angulo
چکیده

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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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015