Elucidating progesterone effects in breast cancer: Cross talk with PDGF signaling pathway in smooth muscle cell
Article first published online: 3 AUG 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 100, Issue 1, pages 174–183, 1 January 2007
How to Cite
Soares, R., Guerreiro, S. and Botelho, M. (2007), Elucidating progesterone effects in breast cancer: Cross talk with PDGF signaling pathway in smooth muscle cell. J. Cell. Biochem., 100: 174–183. doi: 10.1002/jcb.21045
- Issue published online: 13 DEC 2006
- Article first published online: 3 AUG 2006
- Manuscript Accepted: 1 JUN 2006
- Manuscript Received: 20 SEP 2005
- “FCT, POCTI and FEDER: Programa Comunitário de Apoio” and “Comissão de Fomento da Investigação em Cuidados de Saúde”, Portuguese Health Ministry. Grant Number: Health Ministry: 218/2001
- breast cancer;
- hormonal signaling;
- smooth muscle cells
Several studies indicate that progesterone exerts relevant effects in breast tissue. However, the exact role of this steroid in breast cancer development and progression has not been elucidated. Here, we show that platelet-derived growth factor (PDGF)-A is one of the progesterone target genes on breast cancer MCF7 and T47D cells. A paracrine role for PDGF-A was investigated, since its receptor expression was down-regulated from breast cancer cells. Progesterone increased PDGF-A protein release as evaluated by Western blotting and ELISA. Medium from Progesterone-treated MCF7 cells resulted in phosphorylation of smooth muscle cells PDGF receptor α. This effect was not observed after treatment with PDGF inhibitor. MCF7 cells-secreted PDGF-A was able to increase smooth muscle cell viability and proliferation and decrease apoptosis, effects that were prevented by the use of a PDGF-A neutralizing antibody. Notably, cell invasion was not influenced by PDGF-A secreted by MCF7 cells. Our results elucidated for the first time the cross talk between progesterone and PDGF signaling pathway. The fact that MCF7-secreted PDGF elicited crucial roles in vascular wall smooth muscle cells, suggested a paracrine pathway for progesterone. Targeting these progesterone-induced processes may provide novel therapeutic strategies for hormone-dependent human breast cancer. J. Cell. Biochem. 100: 174–183, 2007. © 2006 Wiley-Liss, Inc.