Accession Number : ADA566991


Title :   Structure and Function of the Splice Variants of TMPRSS2-ERG, a Prevalent Genomic Alteration in Prostate Cancer


Descriptive Note : Final rept. 15 Aug 2008-14 Aug 2012


Corporate Author : HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE BETHESDA MD


Personal Author(s) : Srivastava, Shiv


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a566991.pdf


Report Date : Sep 2012


Pagination or Media Count : 85


Abstract : We hypothesized that specific ERG splice forms in TMPRSS2-ERG fusion transcripts are selectively expressed in CaP cells and are functionally relevant in CaP. The specific aims of this study were to characterize full length sequences of TMPRSS2-ERG transcripts; to quantitatively evaluate selected TMPRSS2-ERG variants in CaP specimens and their prognostic features; and to defined the functional significance of specific splice variants of the rearranged ERG locus in CaP. We have identified two types of TMPRSS2-ERG,Type I, which encodes full-length ERG protein consisting SAM and ETS domains (ERG1, ERG2, ERG3), and Type II, encoding ERG proteins lacking the ETS domain (ERG8 and a new variant, TEPC). Increased ratio of Type I over Type II variants showed a correlation with poorly differentiated pathology /high Gleason score and outcome. We found that ERG3 a product of Type I splice variant, transcriptionally activates gene expression through ETS-regulated enhancers and ERG8 encoded by the Type II splice variant abrogated the transcriptional activator function of ERG3. We have generated an anti-ERG antibodies to detect the protein products of both Type I and Type II splice variants and demonstrated the correlation between detecting ERG genomic rearrangement and ERG oncoprotein human prostate tumors. We showed that Type I/Type II ERG ratios may play a role in defining the levels of C-MYC oncogene in a TMPRSS2-ERG fusion harboring prostate cancer cell culture model and revealed that Type I/Type II ratio correlated with C-MYC levels, higher Gleason sum and poor overall prognosis of prostate cancer patients.


Descriptors :   *CULTURES(BIOLOGY) , *PROSTATE CANCER , *SPLICES , *TRANSCRIPTION(GENETICS) , CELLS(BIOLOGY) , CODING , LOCUS , NEOPLASMS , PATIENTS , PROSTATE GLAND , SEQUENCES


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE