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Cells 2018, 7(5), 41; https://doi.org/10.3390/cells7050041

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

1
Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Ft. Lauderdale, FL 33314, USA
2
College of Pharmacy, Health Professions Division, Nova Southeastern University, Ft. Lauderdale, FL 33314, USA
3
College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University, Riyadh 13317, Saudi Arabia
4
Post Graduate and Research Department of Biochemistry, Rajah Serfoji Government College, Thanjavur, TN 613005, India
5
College of Pharmacy, King Saud University, Riyadh 12371, Saudi Arabia
6
VRR Institute of Biomedical Sciences, Kattupakkam, Chennai, TN 600056, India
*
Author to whom correspondence should be addressed.
Received: 3 April 2018 / Revised: 2 May 2018 / Accepted: 5 May 2018 / Published: 10 May 2018
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Abstract

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. View Full-Text
Keywords: MDM2; THBS1; MMP9; Angiogenesis; LNCaP-MST; PCR array; Nutlin-3 MDM2; THBS1; MMP9; Angiogenesis; LNCaP-MST; PCR array; Nutlin-3
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Venkatesan, T.; Alaseem, A.; Chinnaiyan, A.; Dhandayuthapani, S.; Kanagasabai, T.; Alhazzani, K.; Dondapati, P.; Alobid, S.; Natarajan, U.; Schwartz, R.; Rathinavelu, A. MDM2 Overexpression Modulates the Angiogenesis-Related Gene Expression Profile of Prostate Cancer Cells. Cells 2018, 7, 41.

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