College of Pharmacy, Duksung Women's University, Seoul 132-714, Korea.
Int J Oncol. 2010 Feb;36(2):501-7.
Overexpression of ErbB2 has been frequently found in mammary carcinoma. We have previously shown that the aberrant activation of H-Ras induces human breast cell invasion and migration. The present study was aimed at investigating the effect of ErbB2 overexpression on H-Ras-induced breast cell invasion and to elucidate the underlying mechanisms. Herein, we show that overexpression of ErbB2 promotes invasive and migratory abilities of H-Ras-activated MCF10A human breast epithelial cells through upregulation of matrix metalloproteinase (MMP)-13 and urokinase-type plasminogen activator (uPA). We also demonstrate that the p38 MAPK is an important signaling molecule in the ErbB2-induced upregulation of MMP-13 and uPA and invasion/migration of H-Ras MCF10A cells overexpressing ErbB2. The present study elucidating the molecular mechanism underlying ErbB2-induced promotion of H-Ras MCF10A cell invasion may provide invaluable information for understanding breast cancer progression and establishing therapeutic interventions for breast cancer.
ErbB2 的过表达在乳腺癌中经常被发现。我们之前已经表明，H-Ras 的异常激活诱导人乳腺细胞侵袭和迁移。本研究旨在探讨 ErbB2 过表达对 H-Ras 诱导的乳腺细胞侵袭的影响，并阐明其潜在机制。在此，我们显示 ErbB2 的过表达通过上调基质金属蛋白酶（MMP）-13 和尿激酶型纤溶酶原激活物（uPA）促进 H-Ras 激活的 MCF10A 人乳腺上皮细胞的侵袭和迁移能力。我们还证明 p38 MAPK 是 ErbB2 诱导的 MMP-13 和 uPA 上调以及过表达 ErbB2 的 H-Ras MCF10A 细胞侵袭和迁移中的重要信号分子。本研究阐明了 ErbB2 诱导的 H-Ras MCF10A 细胞侵袭促进的分子机制，可能为理解乳腺癌的进展提供有价值的信息，并为乳腺癌的治疗干预建立基础。
