Bradbury Robyn, Jiang Wen G, Cui Yu-Xin
Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff, U.K.
Anticancer Res. 2016 Mar;36(3):1143-51.
BACKGROUND/AIM: Mouse double minute 2 (MDM2) and prostate-specific membrane antigen (PSMA) are currently under investigation as individual therapeutic targets due to their overexpression in many cancer types, as well as their pro-tumorigenic effect on cells. Recently, knockdown of PSMA was linked to a decrease in MDM2 and matrix metalloproteinase 2 (MMP2) and an increase in MMP3 and MMP13 expression. We aimed to assess the link between PSMA, MDM2 and the MMPs in metastatic breast cancer cell lines.
Real-time quantitative polymerase chain reaction (PCR) and western blotting were used to assess siRNA-mediated knockdown of MDM2 and PSMA in MDA-MB-231 and ZR-75.1 breast cancer cells. Assays to assess the growth, adhesion, migration and invasion of the cells following siRNA treatment were undertaken. MMP and tissue inhibitor of matrix metalloproteinases (TIMP) levels were assessed via quantitative PCR.
Knockdown of MDM2 resulted in a decrease in PSMA expression levels and vice versa; although this trend was not replicated at the protein level. Knockdown of each of the molecules resulted in a decrease in growth, adhesion, migration and invasive ability of breast cancer cells. Both knockdowns led to a decrease in MMP2 and an increase in MMP3, -10 and -13 gene expression.
MDM2 and PSMA may co-regulate the expression of certain MMPs and, thus, the functionality of cells in metastatic breast cancer.
背景/目的：小鼠双微体2（MDM2）和前列腺特异性膜抗原（PSMA）目前正作为单独的治疗靶点进行研究，因为它们在许多癌症类型中均有过表达，并且对细胞具有促肿瘤发生作用。最近，PSMA的敲低与MDM2和基质金属蛋白酶2（MMP2）的减少以及MMP3和MMP13表达的增加有关。我们旨在评估转移性乳腺癌细胞系中PSMA、MDM2和基质金属蛋白酶（MMPs）之间的联系。
采用实时定量聚合酶链反应（PCR）和蛋白质印迹法评估siRNA介导的MDA-MB-231和ZR-75.1乳腺癌细胞中MDM2和PSMA的敲低情况。在siRNA处理后，进行了评估细胞生长、黏附、迁移和侵袭的实验。通过定量PCR评估MMP和基质金属蛋白酶组织抑制剂（TIMP）水平。
MDM2的敲低导致PSMA表达水平下降，反之亦然；尽管这种趋势在蛋白质水平上未得到重复。每种分子的敲低均导致乳腺癌细胞的生长、黏附、迁移和侵袭能力下降。两种敲低均导致MMP2减少，MMP3、-10和-13基因表达增加。
MDM2和PSMA可能共同调节某些MMPs的表达，从而调节转移性乳腺癌细胞的功能。
