MDM2 Overexpression Modulates the Angiogenesis-Related Gene Expression Profile of Prostate Cancer Cells

Cells

Aiyavu Chinnaiyan¹  Saad Alobid²  Thiagarajan Venkatesan²  Sivanesan Dhandayuthapani²  Khalid Alhazzani²  Priya Dondapati²  Ali Alaseem²  Thanigaivelan Kanagasabai²  Appu Rathinavelu²  Ruben Schwartz²  Umamaheswari Natarajan³ 

[1] Post Graduate and Research Department of Biochemistry, Rajah Serfoji Government College, Thanjavur, TN 613005, India;Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Ft. Lauderdale, FL 33314, USA;VRR Institute of Biomedical Sciences, Kattupakkam, Chennai, TN 600056, India;

关键词: MDM2;    THBS1;    MMP9;    Angiogenesis;    LNCaP-MST;    PCR array;    Nutlin-3;   

DOI  :  10.3390/cells7050041

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown