Dr. Fraizerâ€™s laboratory uses molecular and genetic approaches to delineate mechanisms of tumor development, including angiogenesis and metastasis. Dr. Fraizerâ€™s research has examined proliferation, migration and gene expression in urologic and hematologic tumors. A major focus is the investigation of angiogenic and metastatic adaptation of prostate cancer cells. Our approach has been to examine regulators of androgen signaling including zinc finger transcription factors such as Sp1 and the Wilms' tumor gene (WT1). Research elucidating the mechanisms of WT1 and Sp1 mediated regulation of the vascular endothelial growth factor (VEGF) in prostate cancer cells grew out of our microarray analyses of RNA obtained from Laser Capture microscopy of prostate tissues and from cultured prostate cancer cells. One long-term goal of the lab is to understand how WT1 and Sp1 alter androgen induction of VEGF. Another is to determine whether WT1 enhances motility by contributing to epithelial-mesenchymal transition (EMT), a process required for metastatic progression. These studies will contribute to identification of pathways utilized in prostate cancer progression/metastasis and may ultimately impact diagnosis and possibly therapy of prostate cancer. A more recent focus for the lab has been motivated by the long suspected but still unknown role of WT1 in hematopoietic cell transformation. We have recently discovered a potential link between WT1 and cell cycle regulators in acute leukemia. These studies could ultimately address the balance between proliferation and differentiation of hematopoietic precursors. Overall the goal of Dr. Fraizerâ€™s research is to delineate tumor mechanisms that provide potential targets for therapy.
1. Brett, A., Pandey, S., Fraizer, G., â€œThe Wilmsâ€™ tumor gene (WT1) regulates E-cadherin expression and migration of prostate cancer cellsâ€ Molecular Cancer 12:3 (2013) doi:10.1186/1476-4598-12-3
2. Kurtis Eisermann, Carly Broderick, Anton Bazarov, Mustafa Moazam, and Gail Fraizer, â€œAndrogen up-regulates vascular endothelial growth factor expressionin prostate cancer cells via an Sp1 binding siteâ€ Molecular Cancer 12:7 (2013) doi:10.1186/1476-4598-12-7
3. Jennifer Gregg and Gail Fraizer, â€œTranscriptional Regulation of EGR1 by EGF and the ERK Signaling Pathway in Prostate Cancer Cellsâ€ Genes & Cancer 1947601911431885, first published on January 24, 2012 doi:10.1177/1947601911431885
4. Gregg JL, Brown KE, Mintz EM, Piontkivska H, Fraizer GC. Analysis of gene expression in prostate cancer epithelial and interstitial stromal cells using laser capture microdissection. BMC Cancer. 2010 Apr 28;10:165. PubMed PMID: 20426842; PubMed Central PMCID: PMC2876079.
5. Joshi B, Chakrabarty A, Bruot C, Ainsworth H, Fraizer G, Wei QH. DNA-WT1protein interaction studied by surface-enhanced Raman spectroscopy. Anal Bioanal Chem. 2010 Feb;396(4):1415-21. PubMed PMID: 20063154.
6. Eisermann K, Tandon S, Bazarov A, Brett A, Fraizer G, Piontkivska H. Evolutionary conservation of zinc finger transcription factor binding sites in promoters of genes co-expressed with WT1 in prostate cancer. BMC Genomics. 2008 Jul 16;9:337. PubMed PMID: 18631392; PubMed Central PMCID: PMC2515153.
7. Ray S, Shyam S, Fraizer GC, Almasan A. S-phase checkpoints regulate Apo2 ligand/TRAIL and CPT-11-induced apoptosis of prostate cancer cells. Mol Cancer Ther. 2007 Apr;6(4):1368-78. PubMed PMID: 17431115.
8. Hanson J, Gorman J, Reese J, Fraizer G. Regulation of vascular endothelial growth factor, VEGF, gene promoter by the tumor suppressor, WT1. Front Biosci. 2007 Jan 1;12:2279-90. PubMed PMID: 17127464; PubMed Central PMCID: PMC2562899.
9. Fraizer G, Leahy R, Priyadarshini S, Graham K, Delacerda J, Diaz M. Suppression of prostate tumor cell growth in vivo by WT1, the Wilms' tumor suppressor gene. Int J Oncol. 2004 Mar;24(3):461-71. PubMed PMID: 14767530.
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