This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Proietti, C. J.
Right arrow Articles by Elizalde, P. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Proietti, C. J.
Right arrow Articles by Elizalde, P. V.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2009, p. 1249-1265, Vol. 29, No. 5
0270-7306/09/$08.00+0     doi:10.1128/MCB.00853-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Activation of Stat3 by Heregulin/ErbB-2 through the Co-Option of Progesterone Receptor Signaling Drives Breast Cancer Growth{triangledown} ,{dagger}

Cecilia J. Proietti,{ddagger} Cinthia Rosemblit,{ddagger} Wendy Beguelin, Martín A. Rivas, María Celeste Díaz Flaqué, Eduardo H. Charreau, Roxana Schillaci, and Patricia V. Elizalde*

Instituto de Biología y Medicina Experimental, CONICET, Obligado 2490, Buenos Aires 1428, Argentina

Received 28 May 2008/ Returned for modification 15 July 2008/ Accepted 4 December 2008

Cross talk between the steroid hormone receptors for estrogen and progesterone (PR) and the ErbB family of receptor tyrosine kinases appears to be a hallmark of breast cancer growth, but its underlying mechanism remains poorly explored. Here we have highlighted signal transducer and activator of transcription 3 (Stat3) as a key protein activated by heregulin (HRG), a ligand of the ErbB receptors, through co-opted, ligand-independent PR function as a signaling molecule. Stat3 activation was an absolute requirement in HRG-induced mammary tumor growth, and targeting Stat3 effectively inhibited growth of breast cancer cells with activated HRG/ErbB-2 and PR. Our findings unravel a novel potential therapeutic intervention in PR- and ErbB-2-positive breast tumors, involving the specific blockage of PR signaling activity.

* Corresponding author. Mailing address: Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), Obligado 2490, Buenos Aires 1428, Argentina. Phone: 5411-4783-2869. Fax: 5411-4786-2564. E-mail: Elizalde{at}dna.uba.ar

{triangledown} Published ahead of print on 22 December 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} C.J.P. and C.R. contributed equally to this paper.

Molecular and Cellular Biology, March 2009, p. 1249-1265, Vol. 29, No. 5
0270-7306/09/$08.00+0     doi:10.1128/MCB.00853-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»