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

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 329卷 / 04期

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

页码：1253 / 1259

页数：7

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