Early growth response-1 gene - Potential radiation response gene marker in prostate cancer

Early growth response-1 gene - Potential radiation response gene marker in prostate cancer
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DOI:
10.1097/00000421-200110000-00017
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发表时间:
2001-10-01
影响因子:
2.6
通讯作者:
Mohiuddin, M
Mohiuddin, M
中科院分区:
医学4区
文献类型:
--
作者:
Ahmed, MM;Chendil, D;Mohiuddin, M

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本研究旨在确定转录因子EGR-1在原发肿瘤中的表达是否与放射反应相关:(1)在肿瘤完全局部控制方面,没有疾病或复发的证据,也没有转移的证据;(2)在放疗后活检组织中与残留肿瘤相关;以及(3)与Egr-1靶基因的表达相关,如TP53、PRB和Bax。作者分析了:(1)25例手术切除石蜡包埋的前列腺癌组织中EGR-1的表达和突变情况。并将其与临床终点相关,如血清前列腺特异性抗原水平和当前临床状态;(2)27例放疗后前列腺活检组织中EGR-1的表达,并将这些发现与残留肿瘤状态相关联;以及(3)12例前列腺癌预期样本中EGR-1表达及其靶基因的检测。免疫组织化学方法检测EGR-1的表达,聚合酶链式反应-单链构象多态性分析检测Egr-1基因的两个区域(反式激活域[TD]的三核苷酸AGC重复序列和3‘非编码区的多聚A区)的突变。25例中有18例表达EGR-1。EGR-1过度表达与治疗失败相关。未发现与EGR-1过度表达及其靶基因的相关性,这可能间接提示过度表达的EGR-1可能缺乏反式激活功能。综上所述,突变形式的EGR-1过表达可能预示着临床失败(局部复发或转移)。
This study was undertaken to determine whether the transcription factor EGR-1 expression: (1) in the primary tumor, correlates with radiation response in terms of complete local tumor control with no evidence of disease or recurrence and no evidence of metastasis; (2) in the postirradiated biopsies correlates with residual tumor; and (3) correlates with the expression of Egr-1 target genes such as TP53, pRB, and Bax. The authors analyzed: ( 1) 25 pretreated surgically resected paraffin-embedded primary adenocarcinomas of the prostate for the presence of EGR-1 expression and mutation. and correlated this with clinical endpoints such as serum prostate-specific antigen levels and current clinical status; (2) 27 postirradiated biopsies of prostate for the presence of EGR-1 expression, and correlated these findings to the residual tumor status; and (3) 12 prospective prostate tumor specimens for EGR-1 expression and its target genes. EGR-1 expression was determined by immunohistochemistry and mutations were screened in two regions of the Egr-1 gene (trinucleotide AGC repeats in transactivation domain [TD] and poly A tract in 3'UTR) by polymerase chain reaction-single strand conformational polymorphism analysis. Of 25 patients, 18 patients showed expression of EGR-1. EGR-1 overexpression correlated with treatment failure. No correlation with EGR-1 overexpression and its target genes was found, which may indirectly suggest that overexpressed EGR-1 may lack transactivation function. In summary, EGR-1 overexpression in the mutant form may provide an indication of clinical failure (local recurrence or metastasis).