MDM2 Overexpression Modulates the Angiogenesis-Related Gene Expression Profile of Prostate Cancer Cells.
MDM2 Overexpression Modulates the Angiogenesis-Related Gene Expression Profile of Prostate Cancer Cells.
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DOI：
10.3390/cells7050041
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发表时间：
2018-05-10
期刊：
影响因子：
6
通讯作者：
Rathinavelu A
中科院分区：
文献类型：
--
作者：
Venkatesan T;Alaseem A;Chinnaiyan A;Dhandayuthapani S;Kanagasabai T;Alhazzani K;Dondapati P;Alobid S;Natarajan U;Schwartz R;Rathinavelu A
小鼠双微体2（MDM 2）基因扩增或过表达在许多具有高转移和血管生成能力的肿瘤中被发现。我们的实验旨在探索MDM 2过表达的影响，特别是对血管生成相关基因水平的影响，这些基因也可以在肿瘤增殖中发挥重要作用并增加其转移潜力。在本研究中，我们使用人血管生成RT 2 profiler PCR阵列来比较LNCaP和LNCaP-MST（MDM 2转染）前列腺癌细胞之间的基因表达谱，沿着用MDM 2特异性抑制剂Nutlin-3处理的LNCaP-MST细胞。MDM 2基因在LNCaP-MST中的过表达（10.3倍）导致血小板反应蛋白1（THBS 1）、肿瘤坏死因子α（TNF-α）和基质金属肽酶9（MMP 9）的表达显著上调，而上皮调节蛋白（EREG）、金属蛋白酶组织抑制剂1（TIMP 1）等基因表达下调。此外，我们还测定了LNCaP、LNCaP-MST和SJSA-1细胞中的总MMP活性和MMP 9表达。我们的结果表明，MDM 2水平与MMP活性和MMP 9分泌呈正相关。我们的研究结果提供了强有力的支持证据，即MDM 2可以通过使平衡向促血管生成机制倾斜来影响癌细胞的生长和转移潜力。
The Murine Double Minute 2 (MDM2) amplification or overexpression has been found in many tumors with high metastatic and angiogenic ability. Our experiments were designed to explore the impact of MDM2 overexpression, specifically on the levels of angiogenesis-related genes, which can also play a major role in tumor propagation and increase its metastatic potential. In the present study, we have used the human angiogenesis RT2 profiler PCR array to compare the gene expression profile between LNCaP and LNCaP-MST (MDM2 transfected) prostate cancer cells, along with LNCaP-MST cells treated with Nutlin-3, an MDM2 specific inhibitor. As a result of the overexpression of MDM2 gene in LNCaP-MST (10.3-fold), Thrombospondin 1 (THBS1), Tumor necrosis factor alpha (TNF-α) and Matrix metallopeptidase 9 (MMP9) were also found to be significantly up-regulated while genes such as Epiregulin (EREG), Tissue inhibitor of metalloproteinases 1 (TIMP1) were down-regulated. Also, we determined the total MMP activity and MMP9 expression in LNCaP, LNCaP-MST and SJSA-1 cells. Our results indicated that MDM2 level is positively correlated with MMP activity and MMP9 secretion. Our findings offer strong supporting evidence that MDM2 can impact growth and metastatic potential of cancer cells through tilting the balance towards pro-angiogenic mechanisms.
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DOI：
10.1146/annurev-pathol-012414-040349
发表时间：
2016-05-23
期刊：
Annual review of pathology
影响因子：
--
作者：
Karni-Schmidt O;Lokshin M;Prives C
通讯作者：
Prives C
MDM2通过诱导基质金属蛋白酶9促进浸润性导管乳腺癌的侵袭和转移
影响因子：
3.7
作者：
Chen, Xiaofeng;Qiu, Jinrong;Yin, Yongmei
通讯作者：
Yin, Yongmei
影响因子：
11.2
作者：
Lowe JM;Menendez D;Bushel PR;Shatz M;Kirk EL;Troester MA;Garantziotis S;Fessler MB;Resnick MA
通讯作者：
Resnick MA
影响因子：
9.7
作者：
Shi, Wei-Dong;Meng, Zhi-Qiang;Liu, Lu-Ming
通讯作者：
Liu, Lu-Ming
影响因子：
4.8
作者：
Orso, Francesca;Penna, Elisa;Taverna, Daniela
通讯作者：
Taverna, Daniela