G. An et al., Human prostate-specific transglutaminase gene: Promoter cloning, tissue-specific expression, and down-regulation in metastatic prostate cancer, UROLOGY, 54(6), 1999, pp. 1105-1111
Objectives. To investigate the tissue-specific and differential expression
of the human prostate-specific transglutaminase (pTGase) gene in metastatic
prostate cancer (CaP) and to study how this gene is regulated in the prost
ate.
Methods, Northern blot hybridization and polymerase chain reaction (PCR) we
re performed using RNA from a variety of organs to confirm prostate-specifi
c expression of the gene. Relative quantitative reverse transcriptase-PCR (
RT-PCR) was performed to investigate the differential expression of the gen
e among normal prostates and prostates with CaP and metastatic CaP. The pTG
ase gene promoter was cloned using genomic library screening and sequencing
. Transfection experiments and chloramphenicol acetyltransferase (CAT) assa
ys were performed to study the regulation of the gene.
Results. Northern hybridization and RT-PCR confirmed that the gene is only
expressed in the prostate, Relative quantitative RT-PCR demonstrated a loss
of expression of the pTGase gene among men with CaP and higher Gleason gra
des. In metastatic CaP tissue from;various: sites, 86% of the samples lost
expression of the gene. We cloned and sequenced a 1.4-kilobase promoter reg
ion of the pTGase gene. Transfection and CAT assay results supported the th
eory that certain elements in:the -1 to -520 region are sufficient to direc
t prostate-specific expression of the gene. Additional elements in the -520
to -1400 region may also Contribute to its prostate-specific expression.
Conclusions. The results of our study demonstrate that the human pTGase gen
e is only expressed in prostate tissue and that its expression is inhibited
in most metastatic CaP. Prostate-specific expression of the gene is contro
lled by elements in the promoter region. The observed preferential loss of
pTGase gene expression in metastatic CaP may be important to the :pathogene
sis and progression of this disease. (C) 1999, Elsevier Science Inc.