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PMID: 12237774 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters.

British journal of cancer ·Vol. 87 ·No. 6 ·2002-09-09 ·Pages 635-44

Fritz G, Brachetti C, Bahlmann F, Schmidt M, Kaina B

Abstract

In the present study, we addressed the question of a putative relevance of Rho proteins in tumour progression by analysing their expression on protein and mRNA level in breast tumours. We show that the level of RhoA, RhoB, Rac1 and Cdc42 protein is largely enhanced in all tumour samples analysed (n=15) as compared to normal tissues originating from the same individual. The same is true for (32)P-ADP-ribosylation of Rho proteins which is catalysed by Clostridium botulinum exoenzyme C3. Also the amount of Rho-GDI and ERK2 as well as the level of overall (32)P-GTP binding activity was tumour-specific elevated, yet to a lower extent than Rho proteins. Although the amount of Rho proteins was enhanced in tumours, most of them did not show changes in rho mRNA expression as compared to the corresponding normal tissue. Thus, elevated gene expression seems not to be the underlying mechanism of tumour-specific overexpression of Rho proteins. Sequence analysis of RhoA, RhoB, RhoC and Rac1 failed to detect any mutations in both the GTP-binding site and effector binding region. By analysing >50 tumour samples, the amount of RhoA-like proteins (i.e. RhoA, B, C), but not of Rac1, was found to significantly increase with histological grade and proliferation index. Rho protein expression was neither related to p53 nor to HER-2/neu oncogene status. Expression of rho mRNAs did not show a significant increase with histological grade. Overall the data show that (1) Rho proteins are overexpressed in breast tumours (2) overexpression is not regulated on the mRNA level (3) the expression level of RhoA-like proteins correlates with malignancy and (4) Rho proteins are not altered by mutation in breast tumours.

MeSH Terms
ADP Ribose Transferases/metabolism Blotting, Western Breast/metabolism Breast Neoplasms/genetics,metabolism,pathology DNA Mutational Analysis Disease Progression Female Gene Expression Guanosine Triphosphate/metabolism Humans Mitogen-Activated Protein Kinase 1/genetics,metabolism Mutation/genetics Polymerase Chain Reaction RNA, Messenger/metabolism cdc42 GTP-Binding Protein/genetics,metabolism rac1 GTP-Binding Protein/genetics,metabolism rho GTP-Binding Proteins/genetics,metabolism rhoA GTP-Binding Protein/genetics,metabolism rhoB GTP-Binding Protein/genetics,metabolism
Chemicals
RNA, Messenger Guanosine Triphosphate ADP Ribose Transferases Mitogen-Activated Protein Kinase 1 cdc42 GTP-Binding Protein rac1 GTP-Binding Protein rho GTP-Binding Proteins rhoA GTP-Binding Protein rhoB GTP-Binding Protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Fritz G
Institute of Toxicology, Division of Applied Toxicology, University of Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany. fritz@mail.uni-mainz.de
Brachetti C
Bahlmann F
Schmidt M
Kaina B
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/sj.bjc.6600510
Email
fritz@mail.uni-mainz.de
Published
2002-09-09
Pages
635-44
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2364248
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjc.6600510 PMC Full Text View journal details
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