Zhang Wei, Du Ye, Jiang Tong, Geng Wei, Yuan Jiuli, Zhang Duo
Department of Cosmetology Plastic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2015 Aug;12(2):2919-25. doi: 10.3892/mmr.2015.3757. Epub 2015 May 7.
Gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19), a novel IFN-β/retinoic acid-inducible gene product, has been identified as a potential tumor suppressor, which is associated with the inhibition of tumor growth. GRIM-19 has been demonstrated to be downregulated in the ovarian tissue of patients with breast cancer, however, its role in breast cancer remains to be fully elucidated. In the present study, a recombinant eukaryotic expression plasmid carrying GRIM-19 was constructed and then transfected into the MCF7 human breast cancer cell line to examine its effects on breast cancer cell growth, migration and invasion using several in vitro approaches. The results demonstrated that upregulation GRIM-19 in the MCF7 cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell apoptosis. Additionally, upregulation of GRIM-19 also suppressed the secretion of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF). It was also demonstrated that the activation of signal transducer and activator of transcription 3 (STAT3) was downregulated by the expression of GRIM-19. These results revealed that overexpression of the GRIM-19 gene may be an effective approach to control the growth and invasion of human breast cancer cells.
类视黄醇-干扰素（IFN）诱导死亡率相关基因19（GRIM-19）是一种新型的IFN-β/视黄酸诱导基因产物，已被确定为一种潜在的肿瘤抑制因子，与肿瘤生长抑制有关。GRIM-19在乳腺癌患者的卵巢组织中已被证明表达下调，然而，其在乳腺癌中的作用仍有待充分阐明。在本研究中，构建了携带GRIM-19的重组真核表达质粒，然后将其转染到MCF7人乳腺癌细胞系中，使用几种体外方法检测其对乳腺癌细胞生长、迁移和侵袭的影响。结果表明，上调MCF7细胞中的GRIM-19可显著抑制细胞增殖、集落形成、迁移和侵袭，并诱导细胞凋亡。此外，GRIM-19的上调还抑制了尿激酶型纤溶酶原激活剂（u-PA）、基质金属蛋白酶（MMP）-2、MMP-9和血管内皮生长因子（VEGF）的分泌。还证明了GRIM-19的表达下调了信号转导和转录激活因子3（STAT3）的激活。这些结果表明，GRIM-19基因的过表达可能是控制人乳腺癌细胞生长和侵袭的有效方法。
