Department of Gerontology and Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Oncol Rep. 2013 May;29(5):1873-80. doi: 10.3892/or.2013.2336. Epub 2013 Mar 6.
Lung cancer is the leading cause of cancer morbidity and mortality in the world. The incidence of lung cancer, particularly lung adenocarcinoma, is increasing in women compared to men. The role of sex hormones in the development of lung cancer has attracted substantial interest, but remains largely unknown. In this study, we demonstrated that membrane progesterone receptor α (mPRα) was expressed in a lung adenocarcinoma cell line, A549, and was located on the cell membrane. In additional experiments, we found that mPRα functioned as an essential mediator for progesterone (P4)-induced inhibitory effects on cell migration and invasion of A549 cells. Furthermore, PP1 (an Src pathway inhibitor), when co-incubated with P4, synchronously enhanced the inhibitory effects of P4 on cell migration and invasion. To explore the mechanisms of inhibition, we found that P4 and PP1 induced a cascade of molecular signaling events, such as dephosphorylation of focal adhesion kinase (FAK) and downregulation of matrix metalloproteinase 9 (MMP-9). Our study provides a mechanistic view on the effects of P4 through mPRα→Src/FAK relevant pathways in human lung adenocarcinoma cells and may aid in the development of novel therapeutic tools for the treatment of lung cancer.
肺癌是世界上癌症发病率和死亡率的主要原因。与男性相比，女性肺癌（尤其是肺腺癌）的发病率正在增加。性激素在肺癌发展中的作用引起了广泛关注，但仍知之甚少。在这项研究中，我们证明了膜孕激素受体α（mPRα）在肺腺癌细胞系 A549 中表达，并位于细胞膜上。在其他实验中，我们发现 mPRα作为孕激素（P4）诱导的对 A549 细胞迁移和侵袭的抑制作用的必需介质起作用。此外，当与 P4 共同孵育时，PP1（Src 途径抑制剂）同步增强了 P4 对细胞迁移和侵袭的抑制作用。为了探索抑制机制，我们发现 P4 和 PP1 诱导了一系列分子信号事件，如粘着斑激酶（FAK）的去磷酸化和基质金属蛋白酶 9（MMP-9）的下调。我们的研究提供了 P4 通过 mPRα→Src/FAK 相关途径在人肺腺癌细胞中的作用的机制观点，并可能有助于开发治疗肺癌的新型治疗工具。
