Detection of HDM2 and VEGF co-expression in cancer cell lines: novel effect of HDM2 antisense treatment on VEGF expression

Narasimhan, Madhusudhanan; Rose, R. Wesley; Muthusamy, Karthikeyan; Rathinavelu, Appu

doi:10.1016/j.lfs.2007.08.029

Cited by 11 publications

(13 citation statements)

References 47 publications

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“…To date some of our own experiments and the reports from other laboratories have clearly demonstrated that overexpression of VEGF could significantly enhance cancer cell survival [13,14]. Accordingly, we have found a correlation for HDM2 in GI-101A, HL-60, MCF-7, A2780/CP70, OVCAR-3 and LNCaP cells with respect to proangiogenic regulatory mechanisms [15]. In general, loss of p53 activity in tumour cells enhances the levels of HIF-1␣ and STAT3 to augment gene transcription in response to hypoxia, including VEGF expression [11,16].…”

Section: Introductionsupporting

confidence: 70%

A novel regulation of VEGF expression by HIF‐1α and STAT3 in HDM2 transfected prostate cancer cells

Rathinavelu¹,

Narasimhan²,

Muthumani³

2012

J Cellular Molecular Medi

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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.

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Section: Introductionsupporting

confidence: 70%

A novel regulation of VEGF expression by HIF‐1α and STAT3 in HDM2 transfected prostate cancer cells

Rathinavelu¹,

Narasimhan²,

Muthumani³

2012

J Cellular Molecular Medi

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“…Narasimhan et al . [25] reported that a mutant-type p53 could enhance VEGF expression induced by 12- O -tetradecanoylphorbol-13-acetate by activating protein kinase C. Cadwell and Zambetti [26] showed that wild-type p53 down-regulates VEGF promoter activity. This study showed that G-CSF treatment increased the HIF-1 mRNA expression level and reduced p53 mRNA expression in CMECs.…”

Section: Discussionmentioning

confidence: 99%

The Effects of G-CSF on Proliferation of Mouse Myocardial Microvascular Endothelial Cells

Zou

et al. 2011

IJMS

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This paper explores the effect of granulocyte colony-stimulating factor (G-CSF) on mouse myocardial microvascular endothelial cell (CMECs) proliferation. CMECs were harvested from C57/BL6 mice. CMECs were cultured in medium containing G-CSF (0 ng/mL, 20 ng/mL, 40 ng/mL, 60 ng/mL) for five days. Proliferative activity of CMECs was examined by CCK-8 method. Hypoxia inducible factor-1 (HIF-1) and p53 expression levels was determined from the mRNA obtained by reverse transcription polymerase chain reaction (RT-PCR). Results showed that the purity quotient of the CMECs, which were cultured by the method of modified myocardial tissue explant culture, was higher than 95%. Compared with control untreated cells, the proliferative activity of CMECs and the expression level of HIF-1 mRNA in these cells were enhanced by G-CSF treatment, whereas the expression level of p53 mRNA was markedly reduced. It may be concluded that G-CSF could promote the proliferative activity of CMECs, which might be mediated by upregulation of HIF-1 and downregulation of p53.

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“…The GI-101A and HL-60 cells used in our experiments were found to overexpress HDM2 and offered an interesting model to study VEGF expression (Narasimhan et al, 2007). The HDM2, a p53 neutralizing protein, is shown to be responsible for influencing growth and metastasis of tumors that lack p53 mutation.…”

Section: Introductionmentioning

confidence: 89%

Identification of HDM2 as a regulator of VEGF expression in cancer cells

Narasimhan¹,

Rose²,

Ramakrishnan³

et al. 2008

Life Sciences

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Detection of HDM2 and VEGF co-expression in cancer cell lines: novel effect of HDM2 antisense treatment on VEGF expression

Cited by 11 publications

References 47 publications

A novel regulation of VEGF expression by HIF‐1α and STAT3 in HDM2 transfected prostate cancer cells

A novel regulation of VEGF expression by HIF‐1α and STAT3 in HDM2 transfected prostate cancer cells

The Effects of G-CSF on Proliferation of Mouse Myocardial Microvascular Endothelial Cells

Identification of HDM2 as a regulator of VEGF expression in cancer cells

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