Quantitative expression of TMPRSS2 transcript in prostate tumor cells reflects TMPRSS2-ERG fusion status.
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.
Mwamukonda
K
K
Urology Service, Department of Surgery, Walter Reed Army Medical Center, Washington, DC, USA.
Chen
Y
Y
Ravindranath
L
L
Furusato
B
B
Hu
Y
Y
Sterbis
J
J
Osborn
D
D
Rosner
I
I
Sesterhenn
I A
IA
McLeod
D G
DG
Srivastava
S
S
Petrovics
G
G
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*
D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C515553:TMPRSS2-ERG fusion protein, human; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human