Rho GDP dissociation inhibitor α expression correlates with the outcome of CMF treatment in invasive ductal breast cancer

被引:10
作者
Ronneburg, Henrike [1 ]
Span, Paul N. [2 ]
Kantelhardt, Eva [1 ]
Dittmer, Angela [1 ]
Schunke, Dario [1 ]
Holzhausen, Hans-Juergen [3 ]
Sweep, Fred C. G. J. [2 ]
Dittmer, Juergen [1 ]
机构
[1] Univ Halle Wittenberg, Klin Gynakol, Halle, Saale, Germany
[2] Radboud Univ Nijmegen, Dept Chem Endocrinol, Med Ctr, NL-6525 ED Nijmegen, Netherlands
[3] Univ Halle Wittenberg, Inst Pathol, Halle, Saale, Germany
关键词
Rho-GDI; breast cancer; drug resistance; Rho-GTPase;
D O I
10.3892/ijo_00000510
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Rho-GDI alpha is an inhibitor of Rho-GTPases, which is involved in cancer progression. Little is known about its role in breast cancer progression. There is evidence, that Rho-GDI alpha may modulate drug resistance of breast cancer cells. To assess the importance of Rho-GDI alpha as a risk factor in invasive ductal breast cancer, cancer specimens of three groups of patients were analyzed for Rho-GDI alpha RNA (group 1, N=72 and group 2, N=73) or protein expression (group 3, N=90). In group 1, patients did not receive any adjuvant treatment, whereas, in groups 2 and 3, patients were treated with anti-estrogens and/or with chemotherapeutical drugs. Rho-GDI alpha RNA levels, measured by RT-PCR from fresh-frozen material, did not correlate with relapse-free survival in Kaplan-Meier analysis, except in a subgroup of CMF-only treated patients. In this subgroup, higher Rho-GDI alpha RNA levels were significantly associated with more favorable prognosis. Immunohistochemical analysis (group 3) confirmed the link between higher Rho-GDIa expression and better outcome. This was again particularly true for the CMF-only treated patients. Cox regression analysis revealed that high Rho-GDI alpha protein expression reduced the risk for a relapse by similar to 3-fold, even if adjusted for grading, tumor size, nodal and estrogen receptor (ER) status. The data suggest that Rho-GDI alpha is beneficial to patients who received adjuvant chemotherapy. Rho-GDI alpha is possibly a useful biomarker to predict the response of breast cancer patients to CMF treatment.
引用
收藏
页码:379 / 386
页数:8
相关论文
共 25 条
[1]   The GTPase rho controls a p53-dependent survival checkpoint during thymopoiesis [J].
Costello, PS ;
Cleverley, SC ;
Galandrini, R ;
Henning, SW ;
Cantrell, DA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) :77-85
[2]   Normalization of gene expression measurements in tumor tissues: comparison of 13 endogenous control genes [J].
de Kok, JB ;
Roelofs, RW ;
Giesendorf, BA ;
Pennings, JL ;
Waas, ET ;
Feuth, T ;
Swinkels, DW ;
Span, PN .
LABORATORY INVESTIGATION, 2005, 85 (01) :154-159
[3]   Historical analysis of PAI-I from its discovery to its potential role in cell motility and disease [J].
Dellas, C ;
Loskutoff, DJ .
THROMBOSIS AND HAEMOSTASIS, 2005, 93 (04) :631-640
[4]   GDIs: central regulatory molecules in Rho GTPase activation [J].
DerMardirossian, C ;
Bokoch, GM .
TRENDS IN CELL BIOLOGY, 2005, 15 (07) :356-363
[5]   β-Actin is not a reliable loading control in Western blot analysis [J].
Dittmer, Angela ;
Dittmer, Juergen .
ELECTROPHORESIS, 2006, 27 (14) :2844-2845
[6]   Parathyroid hormone-related protein regulates tumor-relevant genes in breast cancer cells [J].
Dittmer, Angela ;
Vetter, Martina ;
Schunke, Dario ;
Span, Paul N. ;
Sweep, Fred ;
Thomssen, Christoph ;
Dittmer, Jurgen .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (21) :14563-14572
[7]  
DOVAS A, 2005, BIOCHEM J, V1, P1
[8]   Rho GDP dissociation inhibitor α interacts with estrogen receptor α and influences estrogen responsiveness [J].
El Marzouk, Saad ;
Schultz-Norton, Jennifer R. ;
Likhite, Varsha S. ;
McLeod, Ian X. ;
Yates, John R. ;
Nardulli, Ann M. .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2007, 39 (3-4) :249-259
[9]  
Gildea JJ, 2002, CANCER RES, V62, P6418
[10]  
Goto T, 2006, ONCOL REP, V15, P1265