A kinase-inactive type II TGFβ receptor impairs BMP signaling in human breast cancer cells

被引：23
作者：
Dumont, N
Arteaga, CL
机构：
[1] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 301卷 / 01期
关键词：
transforming growth factor-beta; bone morphogenetic protein; dominant negative type II TGF beta receptor; signaling; MDA-MB-231;
D O I：
10.1016/S0006-291X(02)02977-7
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：
Dominant negative receptor mutants are often utilized in order to abrogate signaling induced by growth factors. We have previously shown that expression of a dominant negative type 11 TGFbeta receptor (dnTbetaRII) in MDA-MB-231 breast cancer cells effectively abrogates TGFbeta signaling. In this letter, we report that expression of dnTbetaRII also impairs BMP2-mediated Smad1 phosphorylation as well as BMP2-mediated Smad-dependent transcriptional responses, resulting in an attenuation of BMP-mediated anti-proliferative effects. The fact that dnTbetaRII not only abrogates TGFbeta signaling but BMP signaling as well has important implications for the interpretation of data in which dominant negative mutants are utilized. (C) 2002 Elsevier Science (USA). All rights reserved.
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收藏
页码：108 / 112
页数：5
相关论文
共 22 条
[1]   Identification of bone morphogenetic proteins and their receptors in human breast cancer cell lines: Importance of BMP2 [J].
Arnold, SF ;
Tims, E ;
McGrath, BE .
CYTOKINE, 1999, 11 (12) :1031-1037
[2]  
Attisano L, 1996, MOL CELL BIOL, V16, P1066
[3]   Integrin β1 signaling is necessary for transforming growth factor-β activation of p38MAPK and epithelial plasticity [J].
Bhowmick, NA ;
Zent, R ;
Ghiassi, M ;
McDonnell, M ;
Moses, HL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (50) :46707-46713
[4]   Expression of a dominant-negative mutant TGF-beta type II receptor in transgenic mice reveals essential roles for TGF-beta in regulation of growth and differentiation in the exocrine pancreas [J].
Bottinger, EP ;
Jakubczak, JL ;
Roberts, ISD ;
Mumy, M ;
Hemmati, P ;
Bagnall, K ;
Merlino, G ;
Wakefield, LM .
EMBO JOURNAL, 1997, 16 (10) :2621-2633
[5]   Bone morphogenetic protein 2 (BMP-2) induces sequential changes of Id gene expression in the breast cancer cell line MCF-7 [J].
Clement, JH ;
Marr, N ;
Meissner, A ;
Schwalbe, M ;
Sebald, W ;
Kliche, KO ;
Höffken, K ;
Wölfl, S .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2000, 126 (05) :271-279
[6]   DPC4 (SMAD4) mediates transforming growth factor-beta 1 (TGF-beta 1) induced growth inhibition and transcriptional response in breast tumour cells [J].
deWinter, JP ;
Roelen, BAJ ;
tenDijke, P ;
vanderBurg, B ;
vandenEijndenvanRaaij, A .
ONCOGENE, 1997, 14 (16) :1891-1899
[7]  
DUMONT N, IN PRESS J BIOL CHEM
[8]   Bone morphogenetic protein-2 blocks MDA MB 231 human breast cancer cell proliferation by inhibiting cyclin-dependent kinase-mediated retinoblastoma protein phosphorylation [J].
Ghosh-Choudhury, N ;
Woodruff, K ;
Qi, WB ;
Celeste, A ;
Abboud, SL ;
Choudhury, GG .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 272 (03) :705-711
[9]  
Gobbi G, 2002, INT J ONCOL, V20, P143
[10]   Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis [J].
Howe, JR ;
Bair, JL ;
Sayed, MG ;
Anderson, ME ;
Mitros, FA ;
Petersen, GM ;
Velculescu, VE ;
Traverso, G ;
Vogelstein, B .
NATURE GENETICS, 2001, 28 (02) :184-187
123