Aggarwal Suruchi, Singh Minu, Kumar Ashok, Mukhopadhyay Tapas
National Centre for Human Genome Studies and Research, Panjab University, Chandigarh, 160014, India.
Department of Systems Biology, Panjab University, Chandigarh, India.
Mol Cell Biochem. 2015 Oct;408(1-2):15-23. doi: 10.1007/s11010-015-2478-z. Epub 2015 Jun 20.
Steroid 5-alpha reductase type 2 (SRD5A2) gene is important for normal development and functioning of prostate gland but it is reported to be silenced in metastatic prostate cancer. We showed that exogenous SRD5A2 expression in prostate cancer cell line reduced cell migration and invasion. Additionally, the stable transfectants showed enhanced adhesion to the matrix accompanied by changes in cytoskeletal organization, involving actin polymerization. siRNA knockdown of the endogenous SRD5A2 mRNA in LnCAP cells was effective, it reversed the phenotype, and thus induced cell motility. The MEK1 and pERK1/2 levels were found to be reduced in SRD5A2-expressing cells. Further, the reduced level of p38 protein was correlated with low expression of MMP-2 and MMP-7 genes. The results suggest that SRD5A2 controls cell migration by indirectly regulating ERK/MAPK pathway.
类固醇5-α还原酶2型（SRD5A2）基因对前列腺的正常发育和功能很重要，但据报道在转移性前列腺癌中该基因会沉默。我们发现，在前列腺癌细胞系中外源表达SRD5A2可降低细胞迁移和侵袭能力。此外，稳定转染子显示出对基质的黏附增强，同时伴随着细胞骨架组织的变化，涉及肌动蛋白聚合。在LnCAP细胞中对内源性SRD5A2 mRNA进行siRNA敲低是有效的，它逆转了表型，从而诱导细胞运动。在表达SRD5A2的细胞中发现MEK1和pERK1/2水平降低。此外，p38蛋白水平的降低与MMP-2和MMP-7基因的低表达相关。结果表明，SRD5A2通过间接调节ERK/MAPK途径来控制细胞迁移。
