Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma

Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma
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DOI:
10.1002/cncr.21639
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发表时间:
2006-02-01
期刊:
影响因子:
6.2
通讯作者:
Noguchi, M
Noguchi, M
中科院分区:
医学1区
文献类型:
--
作者:
Tanaka, R;Ishiyama, T;Noguchi, M

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背景资料。程序性细胞死亡或细胞凋亡的调节对于正常发育和维持体内平衡至关重要。新发现的抗凋亡蛋白Bax-1(BI-1)是一种受Bcl2和Bax1调控的新型细胞死亡途径调节因子。方法32例周围腺癌患者手术切除肺组织标本,检测BI-1基因表达,并与P53、bcl2和Bax基因表达进行比较。癌组织中BI-1基因的表达在腺癌伴细支气管肺泡癌(BAC)和混合亚型腺癌伴细支气管肺泡扩散(14/17,82.4%)明显高于未扩散的癌组织。与BI-1阴性的腺癌患者相比,BI-1阳性的腺癌患者的预后相对较好。P53蛋白阳性11例(34.4%),Bcl2阳性1例(3.1%),Bax阳性26例(81.3%)。免疫组织化学检测P53、Bcl2和Bax蛋白表达与BI-1基因表达无关。结论:BI-1基因的表达仅限于恶性生长的肿瘤细胞,是周围型腺癌的预后因素。目前认为BI-1基因的表达在进化上是保守的,可能是BAC细胞凋亡途径的关键调节因子。
BACKGROUND. The regulation of programmed cell death, or apoptosis, is crucial for normal development and for the maintenance of homeostasis. It has been shown that the novel antiapoptotic protein Bax inhibitor-1 (BI-1) represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax.METHODS. Surgically resected lung specimens were obtained from 32 patients with peripheral adenocarcinomas, and BI-1 gene expression was examined and compared with expression of the p53, bcl-2 and Bax genes.RESULTS. Fourteen of 32 tumors (43.8%) were positive for BI-1 gene expression by in situ hybridization. BI-1 gene expression in tumor specimens was significantly higher in adenocarcinomas with bronchioloalveolar carcinoma (BAC) and in adenocarcinomas of mixed subtypes with bronchioloalveolar spreading (14 of 17 tumors; 82.4%) than in carcinomas without it spreading. Patients who had BI-1-positive adenocarcinoma showed a relatively favorable prognosis compared with patients who had BI-1-negative adenocarcinoma. Eleven of 32 tumors (34.4%) were positive for the p53 protein, only 1 of 32 tumors (3.1%) was positive for the Bcl-2 protein, and 26 of 32 tumors (81.3%) were positive for the Bax protein. Protein expressions of p53, Bcl-2, and Bax, as detected by immunohistochemistry, were not associated with BI-1 gene expression.CONCLUSIONS. BI-1 gene expression was restricted to tumor cells with lepidic growth and was a prognostic factor for peripheral-type adenocarcinoma. It is believed that BI-1 gene expression is conserved evolutionarily and may act as a key regulator of the apoptotic pathway in BAC.