Frequent and early loss of the EGR1 corepressor NAB2 in human prostate carcinoma
Frequent and early loss of the EGR1 corepressor NAB2 in human prostate carcinoma
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DOI：
10.1053/hupa.2001.27102
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发表时间：
2001-09-01
期刊：
影响因子：
3.3
通讯作者：
Milbrandt, J
中科院分区：
文献类型：
--
作者：
Abdulkadir, SA;Carbone, JM;Milbrandt, J
转录因子EGR1在人类前列腺癌中经常过表达，并调节几种对肿瘤进展重要的基因的表达。此外，缺乏Egr1基因的小鼠在前列腺肿瘤发生中表现出缺陷。NAB2是一种调节EGR1活性的新型辅抑制分子，可由诱导EGR1的相同刺激诱导。人类NAB2基因定位于12q13.3-14.1，位于一个被认为含有前列腺肿瘤抑制因子的染色体区域。我们检测了NAB2在人前列腺癌标本中的表达。我们在这里表明，在大多数原发性前列腺癌标本中，包括许多具有高EGR1水平的标本中，NAB2蛋白表达缺失。这种丧失发生在肿瘤形成过程的早期，并持续存在，正如在前列腺上皮内瘤变前体病变和转移中所见。此外，NAB2的缺失与肿瘤分级或分期无关。我们的研究结果表明，高水平的EGR1加上低水平的NAB2可以导致人类前列腺癌中高水平的、不受限制的EGR1转录活性。W.B. Saunders Company版权所有(C) 2001
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. Copyright (C) 2001 by W.B. Saunders Company