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The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells

Brett, Adina R.
http://rave.ohiolink.edu/etdc/view?acc_num=kent1325617408

Abstract Details

2012, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Prostate adenocarcinoma is a complex disease and the molecular mechanisms that control its progression are still not well understood. Even though this type of cancer has a high survival rate, once the process of metastasis is established the mortality rate is very low. In an effort to better understand and elucidate the process of metastasis, the effect of WT1 on E-cadherin regulation and migration was tested in prostate cancer cells. An in silico approach was used to identify potential WT1 binding sites in the E-cadherin promoter. Two new predicted binding sites were identified and characterized in LNCaP and PC3 cells, where we observed and quantified binding of WT1 to the E-cadherin proximal promoter in the chromatin of these cell lines in vivo. The effect of WT1 binding was measured in reporter assays and a strong repressive effect of WT1 on E-cadherin promoter activity in prostate cancer cells was found. This repression was due to a newly identified WT1 binding site located at -146 bp from the transcription start site in the E-cadherin proximal promoter. Moreover, over expression of WT1 decreased the levels of E-cadherin mRNA and conversely, silencing of WT1 was shown to increase the E-cadherin mRNA levels. Similarly, there was an inverse relationship between WT1 and E-cadherin mRNA levels in LNCaP and PC3 prostate cancer cells, cells that have very different migratory potential. These findings led us to investigate the impact of WT1 on migration of prostate cancer cells. Our results revealed that over expression of WT1 enhanced migration of LNCaP cells that have a very low migratory potential. Conversely, silencing of WT1 decreased migration of PC3 cells that have a very high migratory potential. Overall these findings suggest a new role of WT1 and place it as a candidate oncogene that could possibly mediate the process of metastasis in prostate cancer.
Gail Fraizer, PhD (Committee Chair)
Jennifer Marcinkiewicz, PhD (Committee Member)
Gary Meszaros, PhD (Committee Member)
Alex Almasan, PhD (Committee Member)
Chu-Che Tsai, PhD (Committee Member)
131 p.
Biomedical Research
WT1; E-cadherin; prostate cancer

Recommended Citations

Citations

  • Brett, A. R. (2012). The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1325617408

    APA Style (7th edition)

  • Brett, Adina. The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells. 2012. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1325617408.

    MLA Style (8th edition)

  • Brett, Adina. "The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells." Doctoral dissertation, Kent State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1325617408

    Chicago Manual of Style (17th edition)

kent1325617408
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© 2012, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.