Elucidating progesterone effects in breast cancer: cross talk with PDGF signaling pathway in smooth muscle cell.
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 alpha. 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.
Soares
Raquel
R
Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal. raqsoa@med.up.pt
Guerreiro
Susana
S
Botelho
Mónica
M
D017209:Apoptosis; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004958:Estradiol / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D019899:Paracrine Communication; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D011374:Progesterone / Q000502:physiology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D011374:Progesterone; D004958:Estradiol; D020796:Receptor, Platelet-Derived Growth Factor alpha