Met nuclear Localization and Signaling in Breast Cancer

Hepatocyte Growth Factor/Met signaling is associated with tumor aggression and poor prognosis in many cancers, including lymph node negative breast carcinomas. High HOP levels have been correlated with worse patient outcome and over-expression of the cytoplasmic region of Met is associated with poor...

Full description

Saved in:
Bibliographic Details
Main Author: Pozner-Moulis, Sharon A
Format: Report
Language:English
Subjects:
Anatomy and Physiology
ANTIBODIES
ATTACK
BREAST CANCER
CELLS(BIOLOGY)
CYTOPLASM
GERM CELLS
GROWTH(PHYSIOLOGY)
LIVER
Medicine and Medical Research
NEOPLASMS
NUCLEI
PREDICTIONS
TISSUES(BIOLOGY)
TRANSLOCATION
TYROSINE
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hepatocyte Growth Factor/Met signaling is associated with tumor aggression and poor prognosis in many cancers, including lymph node negative breast carcinomas. High HOP levels have been correlated with worse patient outcome and over-expression of the cytoplasmic region of Met is associated with poor prognosis in lymph node negative breast carcinomas. Immunohistologic assay, using antibodies to the cytoplasmic domain of Met, show Met in the nucleus in cell lines and in germinal regions of tissues. Cell fractionation of A43 1 and HEK293 cells reveal a 60kDa band recognized by C-terminal antibodies of Met localizing to the nucleus. This 60kDa fragment can be enriched by the presence of proteosome inhibitors and is independent of HOF treatment. GFP fusion proteins of the cytoplasmic domain of Met transfected into HEK293 cells are found in the nucleus while the full length Met-GFP fusion is membranous. Further deletions of the Met-OFP fusions identify a region of the juxtamembrane domain required for nuclear translocation. This work suggests processing of the Met receptor, in a manner similar to ErbB4, resulting in the release of the cytoplasmic domain and its translocation to the nucleus.