Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder.

Abstract:

:Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic significance of RON and/or c-met protein (MET) expression was analysed in a bladder cancer cohort (n=183). There was no evidence of mutation in the kinase domain of RON. Overexpression of RON using an inducible Tet-off system induced increased cell proliferation, motility, and antiapoptosis. Immunohistochemical analysis showed that RON was overexpressed in 60 cases (32.8%) of primary tumours, with 14 (23.3%) showing a high level of expression. Recepteur d'Origine Nantais expression was positively associated with histological grading, larger size, nonpapillary contour, and tumour stage (all P<0.01). In addition, MET was overexpressed in 82 cases (44.8%). Co-expressed RON and MET was significantly associated with decreased overall survival (P=0.005) or metastasis-free survival (P=0.01) in 35 cases (19.1%). Recepteur d'Origine Nantais-associated signalling may play an important role in the progression of human bladder cancer. Evaluation of RON and MET expression status may identify a subset of bladder-cancer patients who require more intensive treatment.

journal_name

Br J Cancer

authors

Cheng HL,Liu HS,Lin YJ,Chen HH,Hsu PY,Chang TY,Ho CL,Tzai TS,Chow NH

doi

10.1038/sj.bjc.6602593

subject

Has Abstract

pub_date

2005-05-23 00:00:00

pages

1906-14

issue

10

eissn

0007-0920

issn

1532-1827

pii

6602593

journal_volume

92

pub_type

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