Research Area: Cancer cells adapt to their host by adjusting gene expression patterns. They acquire new traits not typically found in normal mature cells. Two key “hallmarks” that cancer cells acquire are the induction of blood vessel formation (angiogenesis) and ability to move (metastasize).
Dr. Fraizer’s laboratory uses molecular and genetic approaches to delineate mechanisms of tumor progression in urologic and hematologic tumors. Regulation of gene expression is an area of expertise for our laboratory and key findings include 1) our discovery of the novel involvement of WT1 in regulation of Prostate Cancer (PCa) growth control genes, and 2) a novel mechanism for androgen mediated regulation of the angiogenesis gene, VEGF. Highly aggressive PCa no longer responds to androgen deprivation therapy, but instead progresses to lethal metastatic PCa. To address this clinically important change we focused our research on delineating metastatic pathways and particularly cell adhesion and motility. Key findings include 1) the demonstration that cell communication genes, connexins, regulate PCa cell motility and 2) the novel discovery that WT1 regulates a cell adhesion gene in PCa cells. 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 a cell cycle regulator in acute leukemia. These studies address the balance between proliferation and differentiation of hematopoietic precursors. Overall the goal of Dr. Fraizer’s research is to delineate tumor mechanisms that provide potential targets for therapy.
Sony Pandey, Mustafa Moazam, Nirmala Ghimirey, Steven J. Kuerbitz, Gail C. Fraizer. WT1 regulates Cyclin A1 expression in K562 cells. Onc Rep (in press)
Eisermann K, Fraizer G. The Androgen Receptor and VEGF: Mechanisms of Androgen-Regulated Angiogenesis in Prostate Cancer. Cancers. 2017; 9(4):32
Gail C. Fraizer, Kurtis Eisermann, Sony Pandey , Adina Brett-Morris , Anton Bazarov, Sarah Nock , Nirmala Ghimirey , Steven J. Kuerbitz , “Functional role of WT1 in prostate cancer”, in “WILMS TUMOR” Ed. J Daniels, Codon Publications, Australia, (2016).
Zhang, A., Hitomi, M., Bar-Shain, N., Dalimov, Z., Ellis, L., Velpula, K.K., Fraizer, G., Gourdie, R.G. and Lathia, J.D. Connexin 43 expression is associated with increased malignancy in prostate cancer cell lines and functions to promote migration. Oncotarget 6(13), 11640–11651 (2015)
Brett, A., Pandey, S., Fraizer, G., “The Wilms’ tumor gene (WT1) regulates E-cadherin expression and migration of prostate cancer cells” Molecular Cancer 12:3 (2013) doi:10.1186/1476-4598-12-3, PMID: 23298185
Kurtis Eisermann, Carly Broderick, Anton Bazarov, Mustafa Moazam, and Gail Fraizer, “Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site” Molecular Cancer 12:7(2013) doi:10.1186/1476-4598-12-7, PMID: 23369005
Jennifer Gregg and Gail Fraizer, “Transcriptional Regulation of EGR1 by EGF and the ERK Signaling Pathway in Prostate Cancer Cells” Genes Cancer 2(9):900-9 (2011) PMID: 22593802
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 10:165 (2010), PubMed PMID: 20426842
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. 9:337 (2008). PubMed PMID: 18631392;
- Elements of Genetics
- Molecular Mechanisms of Cancer
- Honors: Readings in Genetics