Discipline: Biological Sciences
Subcategory: Cancer Research
Courtney Mangum - Tougaloo College
Co-Author(s): Keli Xu and Wen-Cheng Chung, Cancer Institute, University of Mississippi Medical Center, Jackson, MS
Lunatic Fringe (Lfng), a Notch modulator, plays a tumor-suppressive role in the prostate. Loss of Lfng causes expansion of stem-like cells in the prostate basal epithelium and increased cell proliferation, which in turn results in prostatic intraepithelial neoplasia (PIN), abnormal morphological structures of epithelial cells. PIN may turn into an aggressive form of prostate cancer (PCa) via epithelial-mesenchymal transition (EMT). EMT is characterized by an up-regulation of mesenchymal marker, Vimentin and down-regulation of epithelial marker, E-Cadherin. Using Probasin-Cre4, we have genetically engineered mice models (GEMMs) with Lfng deletion in combination with the deletion of tumor suppressive p53 or activation of oncogenic Kras. Prior experiments have shown accelerated PIN development in these models; therefore, we hypothesize that Lfng deletion in combination with p53 deletion or Kras activation will accelerate EMT development in GEMMs. After breeding and genotyping, we isolated and dissected prostate tissue from mice with experimental genotypes Pb-Cre4/Lfng/Kras and Pb-Cre4/Lfng/p53, and control genotypes Pb-Cre4/Lfng and Lfng/p53. The Western blot results showed an intense up-regulation of Vimentin and a modest up-regulation in the E-Cadherin expression in the Pb-Cre4/Lfng/p53 mice model, which may suggest EMT in addition to increased epithelial proliferation. However, in opposition to our hypothesis, the Pb-Cre4/Lfng/Kras mice model resulted in up-regulated E-cadherin and down-regulated Vimentin expressions. This does not suggest EMT in this model. Due to the timeliness of mice breeding and prostate cancer progression, more studies will be needed to test for the mechanisms underlying PCa progression in the Lfng/Notch-regulated GEMMs. These preliminary results may show that different pathways are used during pathogenesis of aggressive forms of PCa.
Funder Acknowledgement(s): Start-up funds from the UMMC Cancer Institute, The University of Mississippi Medical Center, HBCU Summer Research Training Program and the Gomez lab. Financial Support: PC131783 (HBCU-UMMC PCRP).
Faculty Advisor: Keli Xu, email@example.com
Role: Animal dissection, breeding, and western blotting