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Human Sprouty1 suppresses growth, migration, and invasion in human breast cancer cells.

机译:Human Sprouty1抑制人乳腺癌细胞的生长,迁移和侵袭。

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摘要

Breast cancer is the most common cancer and the leading cause of cancer death in women worldwide. Expression of human Sprouty1 (hSpry1) gene is downregulated in most breast cancer patients, implicating it as an important tumor suppressor gene. So, we hypothesized that overexpression of hSpry1 gene may suppress breast cancer cell growth, migration, and invasion. Here, we demonstrate that in breast cancer cell lines, MDA-MB-231 and T47D, transfection-induced overexpression of hSpry1 reduced cell population, proliferation, and colony formation in vitro without affecting cell apoptosis. Adhesion molecules act as both positive and negative modulators of cellular migration and invasion. Here, we found that overexpression of hSpry1 enhances the initial establishment events in breast cancer cell adhesion to type IV collagen and vitronectin. Moreover, the overexpression of hSpry1 in the highly invasive MDA-MB-231 breast cancer cells causes a significant reduction in cellular migration and invasion through Matrigel membranes. In addition, we showed that hSpry1 overexpression prevents VEGF secretion. VEGF is essential for primary tumor growth, migration, and invasion. Thus, our study provides a novel mechanism of tumor suppression activity of hSpry1.
机译:乳腺癌是全世界女性中最常见的癌症,也是导致癌症死亡的主要原因。在大多数乳腺癌患者中,人类Sprouty1(hSpry1)基因的表达被下调,暗示其是重要的抑癌基因。因此,我们假设hSpry1基因的过表达可能抑制乳腺癌细胞的生长,迁移和侵袭。在这里,我们证明了在乳腺癌细胞系MDA-MB-231和T47D中,转染诱导的hSpry1的过表达在体外不影响细胞凋亡的情况下减少了细胞数量,增殖和集落形成。粘附分子既充当细胞迁移和侵袭的正调节剂,又充当负调节剂。在这里,我们发现hSpry1的过表达增强了乳腺癌细胞对IV型胶原和玻连蛋白的粘附的初始建立事件。此外,hSpry1在高侵袭性MDA-MB-231乳腺癌细胞中的过表达导致细胞迁移和通过基质胶膜的侵袭显着减少。此外,我们证明了hSpry1的过度表达可阻止VEGF的分泌。 VEGF对于原发性肿瘤的生长,迁移和侵袭至关重要。因此,我们的研究提供了hSpry1抑制肿瘤活性的新机制。

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