Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Clin Exp Metastasis. 2011 Jun;28(5):437-49. doi: 10.1007/s10585-011-9382-z. Epub 2011 Mar 27.
Gli1 is an established oncogene and its expression in Estrogen Receptor (ER) α negative and triple negative breast cancers is predictive of a poor prognosis; however, the biological functions regulated by Gli1 in breast cancer have not been extensively evaluated. Herein, Gli1 was over-expressed or down-regulated (by RNA interference and by expression of the repressor form of Gli3) in the ERα negative, human breast cancer cell lines MDA-MB-231 and SUM1315. Reduced expression of Gli1 in these two cell lines resulted in a decrease in migration and invasion. Gli1 over-expression increased the migration and invasion of MDA-MB-231 cells with a corresponding increase in expression of MMP-11. Silencing MMP-11 in MDA-MB-231 cells that over-expressed Gli1 abrogated the Gli1-induced enhancement of migration and invasion. Sustained suppression of Gli1 expression decreased growth of MDA-MB-231 in vitro by increasing apoptosis and decreasing proliferation. In addition, silencing of Gli1 reduced the numbers and sizes of pulmonary metastases of MDA-MB-231 in an in vivo experimental metastasis assay. In summary, Gli1 promotes the growth, survival, migration, invasion and metastasis of ERα negative breast cancer. Additionally, MMP-11 is up-regulated by Gli1 and mediates the migration and invasion induced by Gli1 in MDA-MB-231.
Gli1 是一种已确立的癌基因，其在雌激素受体 (ER)α 阴性和三阴性乳腺癌中的表达预示着预后不良；然而，Gli1 在乳腺癌中调节的生物学功能尚未得到广泛评估。在此，我们在 ERα 阴性的人乳腺癌细胞系 MDA-MB-231 和 SUM1315 中过表达或下调 (通过 RNA 干扰和表达 Gli3 的抑制形式)Gli1。这两个细胞系中 Gli1 的表达减少导致迁移和侵袭减少。Gli1 的过表达增加了 MDA-MB-231 细胞的迁移和侵袭，同时 MMP-11 的表达也相应增加。在过表达 Gli1 的 MDA-MB-231 细胞中沉默 MMP-11 ，则消除了 Gli1 诱导的迁移和侵袭增强作用。持续抑制 Gli1 的表达通过增加细胞凋亡和减少增殖，减少 MDA-MB-231 在体外的生长。此外，沉默 Gli1 减少了体内实验转移模型中 MDA-MB-231 的肺转移的数量和大小。总之，Gli1 促进 ERα 阴性乳腺癌的生长、存活、迁移、侵袭和转移。此外，Gli1 上调 MMP-11，并介导 Gli1 在 MDA-MB-231 中诱导的迁移和侵袭。
