title: Progression of breast tumors is accompanied by a decrease in expression of the Rho guanine exchange factor Tiam1.
abstract: In this study, we investigated the expression level of Ras-homologous (Rho) GTPases and the Rho guanine exchange factor (GEF) T-cell lymphoma invasion and metastasis 1 (Tiam1) in breast tumor specimens (n=106) by immunohistochemistry. Rho and Rho-GEF expression scores were compared to clinically established diagnostic and prognostic parameters. We found that RhoA and RhoB scores slightly increased with tumor grade, whereas the Rac1 score remained unaffected. The most significant effects were observed for the Rac1-specific GEF Tiam1. Tiam1 expression scores significantly decreased with the increase in tumor grade, tumor spreading and proliferation. Furthermore, Tiam1 expression was inversely related to the plasminogen activator inhibitor (PAI-1) and estrogen receptor (ER) expression but not the progesterone receptor (PR) and urokinase plasminogen activator (uPA). A low Tiam1 expression was associated with p53 positivity without being related to HER2/neu status. The data show that Tiam1 expression decreases with the progression of breast carcinomas and is inversely associated with several established breast tumor markers. Therefore, we suggest that Tiam1 counteracts the progression of breast carcinomas and is suitable as a novel breast tumor marker.
authors.affiliation: Department of Toxicology, University of Mainz, D-55131 Mainz, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Stebel
authors.forename: C
authors.initials: C
authors.lastname: Brachetti
authors.forename: M
authors.initials: M
authors.lastname: Kunkel
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: G
authors.initials: G
authors.lastname: Fritz
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis; D020743:rhoB GTP-Binding Protein / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D020662:Guanine Nucleotide Exchange Factors; D017395:Plasminogen Activator Inhibitor 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D016159:Tumor Suppressor Protein p53; D014568:Urokinase-Type Plasminogen Activator; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; C087334:TIAM1 protein, human