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Detection of HDM2 and VEGF co-expression in cancer cell lines: novel effect of HDM2 antisense treatment on VEGF expression.
- Source :
-
Life sciences [Life Sci] 2007 Oct 13; Vol. 81 (17-18), pp. 1362-72. Date of Electronic Publication: 2007 Sep 09. - Publication Year :
- 2007
-
Abstract
- The human homologue of murine double minute 2 (HDM2) oncogene is amplified in approximately 7% of all human cancers. Overexpression of HDM2 protein impairs cell cycle control and confers growth advantage to cancer cells. In several cancers the progression of tumor growth and formation of distant metastases are found to be dependent on tumor angiogenesis, a process that is regulated by vascular endothelial growth factor (VEGF). In this study, we have investigated the co-expression of HDM2 and VEGF in various types of human cancer cell lines and have shown that the co-expression is not cell-type-specific. Furthermore, when different types of cell lines were treated with a HDM2 gene specific antisense phosphorothioate oligodeoxynucleotide (HDMAS5), the expression of VEGF mRNA as well as the levels of VEGF protein was found to be decreased. Interestingly, the higher basal levels of VEGF mRNA and the protein observed in HDM2 transfected LNCaP-MST cells were effectively suppressed by HDMAS5 treatment. On the contrary, the mutant oligodeoxynucleotide containing 4 mismatched bases (M4) did not alter the expression of either HDM2 or VEGF in any of the cell lines tested. In conclusion, our findings are the first time evidence showing that HDM2 and VEGF are co-expressed in various cancer cell lines that have aggressive growth and high metastatic abilities. Furthermore, the decrease in VEGF expression observed at the transcriptional as well as translational levels, subsequent to HDMAS5 treatment of p53 null cells, strongly suggests that HDM2 has a regulatory role on VEGF expression in a p53 independent manner.
- Subjects :
- Blotting, Western
Cell Culture Techniques
Cell Line, Tumor
Electrophoresis, Agar Gel
Electrophoresis, Polyacrylamide Gel
Humans
Proto-Oncogene Proteins c-mdm2 antagonists & inhibitors
Proto-Oncogene Proteins c-mdm2 genetics
RNA, Messenger biosynthesis
RNA, Messenger genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Suppressor Protein p53 metabolism
Vascular Endothelial Growth Factor A antagonists & inhibitors
Vascular Endothelial Growth Factor A genetics
Oligonucleotides, Antisense pharmacology
Phosphorothioate Oligonucleotides pharmacology
Proto-Oncogene Proteins c-mdm2 biosynthesis
Vascular Endothelial Growth Factor A biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0024-3205
- Volume :
- 81
- Issue :
- 17-18
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 17931661
- Full Text :
- https://doi.org/10.1016/j.lfs.2007.08.029