Soares Raquel, Guerreiro Susana, Botelho Mónica
Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
J Cell Biochem. 2007 Jan 1;100(1):174-83. doi: 10.1002/jcb.21045.
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.
多项研究表明，孕酮在乳腺组织中发挥着相关作用。然而，这种类固醇在乳腺癌发生和发展中的确切作用尚未阐明。在此，我们表明血小板衍生生长因子（PDGF）-A是乳腺癌MCF7和T47D细胞上的孕酮靶基因之一。由于其受体表达在乳腺癌细胞中下调，因此对PDGF-A的旁分泌作用进行了研究。通过蛋白质印迹法和酶联免疫吸附测定法评估，孕酮增加了PDGF-A蛋白的释放。来自孕酮处理的MCF7细胞的培养基导致平滑肌细胞PDGF受体α磷酸化。用PDGF抑制剂处理后未观察到这种效应。MCF7细胞分泌的PDGF-A能够增加平滑肌细胞活力和增殖并减少凋亡，这些效应可通过使用PDGF-A中和抗体来预防。值得注意的是，细胞侵袭不受MCF7细胞分泌的PDGF-A的影响。我们的结果首次阐明了孕酮与PDGF信号通路之间的相互作用。MCF7分泌的PDGF在血管壁平滑肌细胞中发挥关键作用这一事实，提示了孕酮的一种旁分泌途径。针对这些孕酮诱导的过程可能为激素依赖性人类乳腺癌提供新的治疗策略。
