title: Quantitative expression of TMPRSS2 transcript in prostate tumor cells reflects TMPRSS2-ERG fusion status.
abstract: TMPRSS2-ERG fusion is the most common oncogenic rearrangement in prostate cancer (CaP). Owing to this chromosomal rearrangement one TMPRSS2 allele loses its promoter, and one of the ETS-related gene (ERG) alleles gains that promoter leading to its overexpression in these tumor cells. Some studies suggest that TMPRSS2, an androgen-regulated type II transmembrane serine protease, may have an effect on CaP progression. We hypothesized that a difference in TMPRSS2 expression may be present in vivo between CaP cells with and without TMPRSS2-ERG fusion, or a compensatory mechanism for the allelic loss of TMPRSS2 may balance that expression difference. Therefore, TMPRSS2 mRNA expression was evaluated in microdissected CaP cells with and without TMPRSS2-ERG fusion in 132 CaP patients and analyzed for its correlation with other androgen receptor (AR)-regulated genes and clinicopathological features. In vivo TMPRSS2 expression correlated with that of other AR-regulated genes, including PSA/KLK3 and PMEPA1, offering potential as AR surrogates. A significantly reduced expression of TMPRSS2 was evident in malignant cells harboring TMPRSS2-ERG fusion, but not in CaP cells without TMPRSS2-ERG fusion, further defining these two genetically distinct types of CaP.
authors: Urology Service, Department of Surgery, Walter Reed Army Medical Center, Washington, DC, USA.
authors: K
authors: K
authors: Mwamukonda
authors: Y
authors: Y
authors: Chen
authors: L
authors: L
authors: Ravindranath
authors: B
authors: B
authors: Furusato
authors: Y
authors: Y
authors: Hu
authors: J
authors: J
authors: Sterbis
authors: D
authors: D
authors: Osborn
authors: I
authors: I
authors: Rosner
authors: I A
authors: IA
authors: Sesterhenn
authors: D G
authors: DG
authors: McLeod
authors: S
authors: S
authors: Srivastava
authors: G
authors: G
authors: Petrovics
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis*; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis*
chemical_list: D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C515553:TMPRSS2-ERG fusion protein, human; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human