Expression of neurotensin and NT1 receptor in human breast cancer:: A potential role in tumor progression
Expression of neurotensin and NT1 receptor in human breast cancer:: A potential role in tumor progression
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DOI：
10.1158/0008-5472.can-06-0450
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发表时间：
2006-06-15
期刊：
影响因子：
11.2
通讯作者：
Forgez, Patricia
中科院分区：
文献类型：
--
作者：
Souaze, Frederique;Dupouy, Sandra;Forgez, Patricia
新的证据支持神经降压素作为一种营养和抗凋亡因子，通过高亲和力神经降压素受体（NT1受体）在几种人类实体瘤中介导其控制。在一系列 51 名浸润性导管乳腺癌患者中，所有肿瘤中 34% 的神经降压素呈阳性，91% 的 NT1 受体呈阳性。我们发现神经降压素和 NT1 受体在大部分 (30%) 导管性乳腺肿瘤中共表达，这表明神经降压素信号级联在乳腺癌进展中发挥了作用。在高度恶性的 MDA-MB-231 人乳腺癌细胞系中，功能性表达的 NT1 受体协调一系列转化功能，包括细胞迁移、侵袭、诱导基质金属蛋白酶 (MMP)-9 转录物和 MMP-9 明胶酶活性。通过沉默 RNA 或使用特定的 NT1 受体拮抗剂 SR48692 来破坏 NT1 受体信号传导，导致这些转化功能的逆转以及裸鼠异种移植的 MDA-MB-231 细胞的肿瘤生长。我们的研究结果支持神经降压素在人类乳腺癌进展中的贡献，并指出开发针对神经降压素或 NT1 受体信号级联的治疗分子的实用性。这些策略将扩大治疗方法的范围，并对特定患者有益。
Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the high-affinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients.