An EGF receptor inhibitor induces RAR-β expression in breast and ovarian cancer cells

被引:22
作者
Grunt, TW [1 ]
Puckmair, K
Tomek, K
Kainz, B
Gaiger, A
机构
[1] Med Univ Vienna, Dept Med 1, Div Oncol, Signaling Networks Program, Vienna, Austria
[2] Med Univ Vienna, Dept Med 1, Div Hematol & Hemostaseol, Vienna, Austria
关键词
cross-talk; EGER inhibitor; ErbB receptors; RAR-beta; retinoid receptors;
D O I
10.1016/j.bbrc.2005.02.104
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inhibition of the epidermal growth factor (EGF)-receptor (EGFR) has become a promising anticancer treatment strategy. In addition, application of retinoids yields encouraging results for cancer prevention and therapy. Many tumors express no or low amounts of retinoic acid receptor-beta 2 (RAR-beta 2) due to epigenetic silencing via DNA hypermethylation. RAR-beta 2 is the main mediator of the antiproliferative effect of retinoids. RAR-beta 2 re-expression causes reversal of transformation, cell cycle arrest, and restoration of retinoid sensitivity. RAR-beta 2 is thus a tumor suppressor. Western blotting, colorimetric in vitro cell proliferation assays, and reverse transcription-polymerase chain reaction demonstrated that the EGFR inhibitor PD153035 not only blocked activation of EGFR and inhibited cell growth. but also stimulated RAR-beta expression in MDA-MB-468 breast and OVCAR-3 ovarian carcinoma cells. Upregulation of RAR-beta by PD153035 was confirmed by real-time reverse transcription-polymerase chain reaction. In contrast, expression of other retinoid receptors and of estrogen receptor-alpha was not affected. PD153035-mediated re-induction of RAR-beta was associated with demethylation of the RAR-beta 2 gene promoter beta 2 as demonstrated by methylation-specific polymerase chain reaction. These novel results on the ErbB/retinoid receptor cross-talk may be useful for designing future anticancer combination regimens. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:1253 / 1259
页数:7
相关论文
共 20 条
[1]   The promise of retinoids to fight against cancer [J].
Altucci, L ;
Gronemeyer, H .
NATURE REVIEWS CANCER, 2001, 1 (03) :181-193
[2]   Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway [J].
Caelles, C ;
González-Sancho, JM ;
Muñoz, A .
GENES & DEVELOPMENT, 1997, 11 (24) :3351-3364
[3]   Gefitinib in pretreated non-small-cell lung cancer (NSCLC):: Analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC [J].
Cappuzzo, F ;
Gregorc, V ;
Rossi, E ;
Cancellieri, A ;
Magrini, E ;
Paties, CT ;
Ceresoli, G ;
Lombardo, L ;
Bartolini, S ;
Calandri, C ;
De Rosa, M ;
Villa, E ;
Crinò, L .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (14) :2658-2663
[4]   A decade of molecular biology of retinoic acid receptors [J].
Chambon, P .
FASEB JOURNAL, 1996, 10 (09) :940-954
[5]  
Cote S, 1998, ANTI-CANCER DRUG, V9, P743
[6]   A SPECIFIC INHIBITOR OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR TYROSINE KINASE [J].
FRY, DW ;
KRAKER, AJ ;
MCMICHAEL, A ;
AMBROSO, LA ;
NELSON, JM ;
LEOPOLD, WR ;
CONNERS, RW ;
BRIDGES, AJ .
SCIENCE, 1994, 265 (5175) :1093-1095
[7]  
Grunt TW, 2004, HORIZ CANC RES, V2, P27
[8]   Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and cisplatin sensitivity of breast cancer cells [J].
Grunt, TW ;
Dittrich, E ;
Offterdinger, M ;
Schneider, SM ;
Dittrich, C ;
Huber, H .
BRITISH JOURNAL OF CANCER, 1998, 78 (01) :79-87
[9]   Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands [J].
Herman, JG ;
Graff, JR ;
Myohanen, S ;
Nelkin, BD ;
Baylin, SB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (18) :9821-9826
[10]  
Lichtner RB, 2001, CANCER RES, V61, P5790