The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells
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Kent State University / OhioLINK
2012
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=kent1325617408 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-kent13256174082021-08-03T05:37:44Z The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells Brett, Adina R. Biomedical Research WT1 E-cadherin prostate cancer 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. 2012-01-06 English text Kent State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=kent1325617408 http://rave.ohiolink.edu/etdc/view?acc_num=kent1325617408 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
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NDLTD |
| topic |
Biomedical Research WT1 E-cadherin prostate cancer |
| spellingShingle |
Biomedical Research WT1 E-cadherin prostate cancer Brett, Adina R. The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells |
| author |
Brett, Adina R. |
| author_facet |
Brett, Adina R. |
| author_sort |
Brett, Adina R. |
| title |
The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells |
| title_short |
The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells |
| title_full |
The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells |
| title_fullStr |
The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells |
| title_full_unstemmed |
The effect of the Wilms' tumor gene 1 (WT1) on E-cadherin regulation and migration of prostate cancer cells |
| title_sort |
effect of the wilms' tumor gene 1 (wt1) on e-cadherin regulation and migration of prostate cancer cells |
| publisher |
Kent State University / OhioLINK |
| publishDate |
2012 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=kent1325617408 |
| work_keys_str_mv |
AT brettadinar theeffectofthewilmstumorgene1wt1onecadherinregulationandmigrationofprostatecancercells AT brettadinar effectofthewilmstumorgene1wt1onecadherinregulationandmigrationofprostatecancercells |
| _version_ |
1719422748259778560 |