Frequent and early loss of the EGR1 corepressor NAB2 in human prostate carcinoma.
The transcription factor EGR1 is frequently overexpressed in human prostate cancer and regulates the expression of several genes important for tumor progression. In addition, mice lacking the Egr1 gene show a defect in prostate tumorigenesis. NAB2 is a novel corepressor molecule that modulates EGR1 activity and is induced by the same stimuli that induce EGR1. The human NAB2 gene has been localized to 12q13.3-14.1, within a chromosomal region that is thought to harbor a prostate tumor suppressor. We have examined the expression of NAB2 in human prostate carcinoma specimens. We show here that NAB2 protein expression is lost in a majority of primary prostate carcinoma specimens, including many samples that have high EGR1 levels. This loss occurs early in the tumorigenic process and is sustained, as it is seen in precursor prostatic intraepithelial neoplasia lesions as well as in metastases. Furthermore, loss of NAB2 did not correlate with the tumor grade or stage. Our findings suggest that high levels of EGR1 coupled with low levels of NAB2 can result in high, unrestrained EGR1 transcriptional activity in human prostate cancers.
Abdulkadir
S A
SA
Department of Pathology and Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Carbone
J M
JM
Naughton
C K
CK
Humphrey
P A
PA
Catalona
W J
WJ
Milbrandt
J
J
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
C491000:NAB2 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins