Rumbaugh Goodwin Institute for cancer research, College of Pharmacy, Health Professions Division, Nova Southeastern University, 3200 S. University drive, Ft. Lauderdale, FL 33328, USA.
Department of Medicine, Division of Hematology and Medical Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
On the basis of increasing roles for HDM2 oncoprotein in cancer growth and progression, we speculated that HDM2 might play a major role in hypoxia-induced metastatic process. For verification of this hypothesis, wild type LNCaP prostate cancer cells and HDM2 transfected LNCaP-MST (HDM2 stably transfected) cells were studied. The data obtained revealed that the HDM2 transfected LNCaP-MST cells possessed the ability to multiply rapidly and show distinct morphological features compared to non-transfected LNCaP cells. During hypoxia HDM2 expression in the LNCaP and LNCaP-MST cells were significantly increased. The LNCaP-MST cells also expressed higher levels of HIF-1α (hypoxia inducible factor-1α) and p-STAT3 even under the normoxic conditions compared to the non-transfected cells. The HIF-1α and p-STAT3 expressions were increased several fold when the cells were subjected to hypoxic conditions. The HIF-1α and p-STAT3 protein expressions observed in HDM2 transfected LNCaP-MST cells were 20 and 15 folds higher respectively, compared to the non-transfected wild type LNCaP cells. These results demonstrate that HDM2 may have an important regulatory role in mediating the HIF-1α and p-STAT3 protein expression during both normoxic and hypoxic conditions. Furthermore, the VEGF expression that is typically regulated by HIF-1α and p-STAT3 were also increased significantly by 136% (P< 0.01) after HDM2 transfection. The overall results point towards a novel ability of HDM2 in regulating HIF-1α and p-STAT3 levels even in normoxic conditions that eventually lead to an up-regulation of VEGF expression.
Written by:
Rathinavelu A, Narasimhan M, Muthumani P. Are you the author?
Reference: J Cell Mol Med. 2011 Oct 18. Epub ahead of print.
doi: 10.1111/j.1582-4934.2011.01472.x
PubMed Abstract
PMID: 22004076
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