title: A novel regulation of VEGF expression by HIF-1α and STAT3 in HDM2 transfected prostate cancer cells.
abstract: 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 from our experiments revealed that the HDM2 transfected LNCaP-MST cells possessed an ability to multiply rapidly and show distinct morphological features compared to non-transfected LNCaP cells. During exposures to hypoxia HDM2 expression in the LNCaP and LNCaP-MST cells was significantly higher compared to the normoxic levels. 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 vascular endothelial growth factor (VEGF) expression that is typically regulated by HIF-1α and p-STAT3 was 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.
authors: Health Professions Division, Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Ft. Lauderdale, FL 33313, USA. appu@hpd.acast.nova.edu
authors: Appu
authors: A
authors: Rathinavelu
authors: Madhusudhanan
authors: M
authors: Narasimhan
authors: Praneetha
authors: P
authors: Muthumani
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2