Overexpression of truncated ERG from TMPRSS2-ERG fusion and prostate cancer development
Melanie Leong1*, Wen-feng Shi2*, Jun Tian2, Ellen Cho1, Abbas Raza1, Saquib A Siddiqi1, Abdulhafez Selim3, Han-chun Chen4, Dianzheng Zhang1,4
1Department of Biochemistry and Molecular Biology and Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA; 2Department of Renal Transplantation, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 3Osteotech Inc, Eatontown, NJ, USA; 4Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan, People’s Republic of China; *These authors contributed equally to this work
Abstract: In men, prostate cancer is one of the most common cancers worldwide and the second leading cause of death among all cancer types in Europe and North America, with the numbers of those affected continuing to increase. Recent studies have identified a recurrent fusion of TMPRSS2 with members of the ETS family of transcription factors in about 80% of prostate cancer tissues. Among them, the TMPRSS2-ERG fusion accounts for approximately 50% of these cases. TMPRSS2 is highly regulated by androgen receptor and the chromosomal rearrangement abnormally induces ERG production by androgen. To investigate the effects of ERG overexpression on its target genes expression and prostate cancer development, plasmids were first constructed by inserting the truncated ERG into an expression vector in the forward or reverse directions. A predicted three-dimensional model of the protein structure of the truncated ERG, along with immunofluorescence assays, suggest that the minor deletion on the N-terminus does not appear to affect the structure or function of ERG. Results from ERG target gene expression profile indicate that TMPRSS2-ERG fusion-induced aberrant ERG overexpression is likely involved in prostate cancer development by enhancing tumor angiogenesis.
Keywords: prostate cancer, androgen receptor, TMPRSS2, ERG, chromosomal translocation
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