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Role of Jade-1 in DNA repair in renal cell carcinoma

Renal cell carcinoma (RCC) is a common and life-threatening cancer. Among RCCS, clear-cell renal cell carcinoma (ccRCC) is the most prevalent type and is highly malignant. ccRCC is initiated by loss of the von Hippel-Lindau tumor suppressor gene VHL. The pVHL protein binds and stabilzes the renal suppressor protein Jade-1 and exerts important growth suppressive activities through Jade-1. Since many solid tumors, like ccRCC, exhibit chromosomal instability and hence have defects in repair of DNA double-strand breaks (DSBs), we sought to determine the roles of Jade-1 and pVHL in these processes to elucidate mechanisms of cancer development. This study focused on the impact of pVHL on Jade-1 localization and expression levels in renal cancer cells by immunofluorescence microscopy and on Jade-1 expression levels by immunoblotting and qPCR when double-strand DNA damage is introduced using doxorubicin, neocarzinostatin or gamma irradiation. Early results suggested but do not yet confirm that there are differences in Jade-1 localization and expression levels in response to DNA DSBs in renal cells and renal cancer cells with versus without wild-type pVHL. More experiments are required to draw conclusions from these early data.

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/36586
Date13 June 2019
CreatorsNiu, Leili
ContributorsCohen, Herbert T., McKnight, C. James
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

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